Improvement in laboratory diagnosis of wound botulism and tetanus among injecting illicit-drug users by use of real-time PCR assays for neurotoxin gene fragments.

PubMed

Akbulut, D; Grant, K A; McLauchlin, J

2005-09-01

An upsurge in wound infections due to Clostridium botulinum and Clostridium tetani among users of illegal injected drugs (IDUs) occurred in the United Kingdom during 2003 and 2004. A real-time PCR assay was developed to detect a fragment of the neurotoxin gene of C. tetani (TeNT) and was used in conjunction with previously described assays for C. botulinum neurotoxin types A, B, and E (BoNTA, -B, and -E). The assays were sensitive, specific, rapid to perform, and applicable to investigating infections among IDUs using DNA extracted directly from wound tissue, as well as bacteria growing among mixed microflora in enrichment cultures and in pure culture on solid media. A combination of bioassay and PCR test results confirmed the clinical diagnosis in 10 of 25 cases of suspected botulism and two of five suspected cases of tetanus among IDUs. The PCR assays were in almost complete agreement with the conventional bioassays when considering results from different samples collected from the same patient. The replacement of bioassays by real-time PCR for the isolation and identification of both C. botulinum and C. tetani demonstrates a sensitivity and specificity similar to those of conventional approaches. However, the real-time PCR assays substantially improves the diagnostic process in terms of the speed of results and by the replacement of experimental animals. Recommendations are given for an improved strategy for the laboratory investigation of suspected wound botulism and tetanus among IDUs.

Tetanus

MedlinePlus

... CDC.gov . Recommend on Facebook Tweet Share Compartir Tetanus is an infection caused by bacteria called Clostridium tetani . When the bacteria invade the body, they produce a poison (toxin) that causes painful muscle contractions. Another name for tetanus is “lockjaw”. It often causes a person’s neck ...

Clinical and laboratory characteristics of neonatal hypocalcemia

PubMed Central

Cho, Won Im; Yu, Hyeoh Won; Shin, Choong Ho; Yang, Sei Won; Choi, Chang Won; Kim, Beyong Il

2015-01-01

Purpose To describe the clinical characteristics of full-term neonates with hypocalcemia and to suggest factors associated with neonatal hypocalcemia Methods The medical records of full-term neonates with hypocalcemia were reviewed. Hypocalcemia was defined as an ionized calcium (iCa) concentration of <4 mg/dL. Parathyroid hormone (PTH) insufficiency was defined as a serum PTH level of <60 pg/mL or a serum phosphorus level higher than the serum calcium level in the presence of hypocalcemia. Results Fifty-three neonates were enrolled. The median age at diagnosis of hypocalcemia was 3 days. In all the neonates, formula feeding predominance was observed. Thirty-eight neonates (69.8%) were compatible with PTH insufficiency. The number of formula-fed neonates was significantly higher than that of breast-fed patients among neonates with PTH insufficiency (P=0.017). Intact PTH was negatively correlated with serum phosphorus levels. Twelve out of 14 neonates (85.7%) had 25-hydroxy vitamin D (25OHD) levels <20 ng/mL and 9 neonates (64.3%) had 25OHD levels <10 ng/mL. Twenty-one neonates had hypocalcemic tetany. The serum calcium and iCa concentrations of neonates with tetany were 4.2-8.3 mg/dL and 1.85-3.88 mg/dL, respectively. Three neonates showed symptomatic hypocalcemia with calcium levels over 7.5 mg/dL. Among the 16 neonates who underwent electroencephalography (EEG), 12 had abnormalities, which normalized after 1-2 months. Conclusion Formula milk feeding, PTH insufficiency and low serum vitamin D concentration are associated with the development of neonatal hypocalcemia. Symptoms such as tetany and QT interval prolongation can develop in relatively mild hypocalcemia. Moreover, transient neonatal hypocalcemia can cause transient EEG abnormalities. PMID:26191512

Narrative review: tetanus-a health threat after natural disasters in developing countries.

PubMed

Afshar, Majid; Raju, Mahesh; Ansell, David; Bleck, Thomas P

2011-03-01

Tetanus is an expected complication when disasters strike in developing countries, where tetanus immunization coverage is often low or nonexistent. Collapsing structures and swirling debris inflict numerous crush injuries, fractures, and serious wounds. Clostridium tetani infects wounds contaminated with dirt, feces, or saliva and releases neurotoxins that may cause fatal disease. Clusters of infections have recently occurred after tsunamis and earthquakes in Indonesia, Kashmir, and Haiti. The emergency response to clusters of tetanus infections in developing countries after a natural disaster requires a multidisciplinary approach in the absence of an intensive care unit, readily available resources, and a functioning cold-chain system. It is essential that injured people receive immediate surgical and medical care of contaminated, open wounds with immunization and immunoglobulin therapy. Successful treatment of tetanus depends on prompt diagnosis of clinical tetanus, treatment to ensure neutralization of circulating toxin and elimination of C. tetani infection, control of spasms and convulsions, maintenance of the airway, and management of respiratory failure and autonomic dysfunction.

Treatment of severe life threatening hypocalcemia with recombinant human teriparatide in patients with postoperative hypoparathyroidism - a case series.

PubMed

Andrysiak-Mamos, Elżbieta; Żochowska, Ewa; Kaźmierczyk-Puchalska, Agnieszka; Popow, Michał; Kaczmarska-Turek, Dorota; Pachucki, Janusz; Bednarczuk, Tomasz; Syrenicz, Anhelli

2016-01-01

Hypocalcaemia is a common postoperative complication, both after the resection of parathyroid adenoma associated with primary hyperparathyroidism and after total thyroidectomy due to thyroid cancer or nodular goitre. For a few years, in patients with postoperative hypoparathyroidism and severe hypocalcaemia, who cannot discontinue intravenous calcium preparations even with the use of high vitamin D doses, attempts have been made to add recombinant human parathormone (rhPTH) to the treatment schedule. In this work, for the first time in Poland, we demonstrate the potential use of teriparatide for the treatment of severe hypocalcaemia based on three different cases of postoperative hypoparathyroidism. Case 1. Female (52) with postoperative hypoparathyroidism, after total thyroidectomy and the removal of lower left parathyroid gland due to hyperparathyroidism, several weeks after the surgery still required intravenous calcium infusions because of tetany symptoms. Just one month of teriparatide treatment at 20 μg/0.08 mL given in daily subcutaneous injections proved sufficient to control calcium levels with oral calcium and vitamin D preparations during the next few days until total resolution of hypocalcaemia symptoms and the achievement and maintenance of laboratory normocalcaemia in the following weeks. Female (33) with hypoparathyroidism following total thyroidectomy in 1996 because of papillary thyroid cancer, with congenital tubulopathy associated with renal loss of calcium and magnesium, and the symptoms of tetany recurring since the day of surgery, requiring intravenous calcium administration every 2-3 days. Currently, the patient has been hospitalised because of venous port infection, the only venous access, which made intravenous therapy impossible. Because of the life-threatening condition of the patient, bridging teriparatide treatment was prepared (20 μg/0.08 mL). Complete resolution of clinical symptoms of hypocalcaemia was obtained with teriparatide doses given every 8-12 hours, which made dose reduction possible. Case 3. Female (52) after major oncological surgery because of laryngopharyngeal and cervical oesophageal cancer with the removal of parathyroid glands, fed through PEG, was admitted to hospital with the symptoms of tetany. Despite treatment intensification, the patient experienced a hypocalcaemic crisis during hospitalisation. Teriparatide treatment at 2 × 20 μg/day resulted in the resolution of tetany symptoms, with gradual normalisation of calcium-phosphate balance parameters during the following days. Based on the analysis of these cases, the conclusion was drawn that the use of recombinant human teriparatide allows for the control of severe hypocalcaemia requiring intravenous infusions of calcium in patients with postoperative hypoparathyroidism. (Endokrynol Pol 2016; 67 (4): 403-412).

An unexpected tetanus case.

PubMed

Ergonul, Onder; Egeli, Demet; Kahyaoglu, Bulent; Bahar, Mois; Etienne, Mill; Bleck, Thomas

2016-06-01

1 million cases of tetanus are estimated to occur worldwide each year, with more than 200 000 deaths. Tetanus is a life-threatening but preventable disease caused by a toxin produced by Clostridium tetani-a Gram-positive bacillus found in high concentrations in soil and animal excrement. Tetanus is almost completely preventable by active immunisation, but very rarely unexpected cases can occur in individuals who have been previously vaccinated. We report a case of generalised tetanus in a 22-year-old woman that arose despite the protective antitoxin antibody in her serum. The patient received all her vaccinations in the USA; her last vaccination was 6 years ago. The case was unusual because the patient had received all standard vaccinations, had no defined port of entry at disease onset, and had symptoms lasting for 6 months. Tetanus can present with unusual clinical forms; therefore, the diagnosis and management of this rare but difficult disease should be updated. In this Grand Round, we review the clinical features, epidemiology, treatment, and prognosis of C tetani infections. Copyright © 2016 Elsevier Ltd. All rights reserved.

Postoperative hypocalcemia after thyroidectomy for Graves' disease.

PubMed

Pesce, Catherine E; Shiue, Zita; Tsai, Hua-Ling; Umbricht, Christopher B; Tufano, Ralph P; Dackiw, Alan P B; Kowalski, Jeanne; Zeiger, Martha A

2010-11-01

It is believed that patients who undergo thyroidectomy for Graves' disease are more likely to experience postoperative hypocalcemia than patients undergoing total thyroidectomy for other indications. However, no study has directly compared these two groups of patients. The aim of this study was to determine whether there was an increased incidence or severity of postoperative hypocalcemia in patients who underwent thyroidectomy for Graves' disease. An institutional review board-approved database was created of all patients who underwent thyroidectomy from 1998 to 2009 at the Johns Hopkins Hospital. There were a total of 68 patients with Graves' disease who underwent surgery. Fifty-five patients who underwent total thyroidectomy were randomly selected and served as control subjects. An analysis was conducted that examined potential covariates for postoperative hypocalcemia, including age, gender, ethnicity, preoperative alkaline phosphatase level, size of goiter, whether parathyroid tissue or glands were present in the specimen, and the reason the patient underwent surgery. Specific outcomes examined were calcium levels on postoperative day 1, whether or not patients experienced symptoms of hypocalcemia, whether or not Rocaltrol was required, the number of calcium tablets prescribed upon discharge, whether or not postoperative tetany occurred, and calcium levels 1 month after discharge. Each outcome was analyzed using a logistic regression. Graves' disease patients had a significantly (p-value < 0.001) higher odds of greater number of calcium tablets prescribed upon discharge. Further, 6 of 68 patients with Graves' disease and no patient in the control group were readmitted with tetany (p = 0.033). There was a trend, though not significant, toward patients with Graves' disease having a higher prevalence of hypocalcemia the day after thyroidectomy and 1 month later. Patients with Graves' disease are more likely to require increased dosages of calcium as well as experience tetany postoperatively than patients undergoing total thyroidectomy for other indications. This suggests that patients operated upon for Graves' disease warrant close followup as both inpatients and outpatients for signs and symptoms of hypocalcemia.

Targeting Mucosal Dendritic Cells with Microbial Antigens from Probiotic Lactic Acid Bacteria

DTIC Science & Technology

2008-03-01

Lactoba- cillus gasseri, Lactobacillus plantarum , Lactobacillus delbreuckii, Lactobacillus rhamnosus, Lactobacillus salivarius and Lactobacillus ... Lactobacillus plantarum Helicobacter pylori UreB Mouse [105] S. pneumoniae PsaA Mouse [104] Lactococcus lactis C. tetani TTFC Mouse [81...anthracis (the causative agent of anthrax). An antigen-specific immune response can be elicited using specific strains of Lactobacillus acidophilus

Bone scintigraphy for neonatal osteomyelitis: simulation by extravasation of intravenous calcium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Balsam, D.; Goldfarb, C.R.; Stringer, B.

Intravenously administered calcium gluconate has become increasingly popular in the treatment of neonatal tetany. Occasionally, extravasation results in cellulitis, leading to a clinical diagnosis of superimposed osteomyelitis. Osseous scintigraphy, as the accepted modality in the early detection of osteomyelitis, would tend to be used in this circumstance. This case illustrates a false-positive result, probably due to soft-tissue calcification.

Refractory status epilepticus after inadvertent intrathecal injection of tranexamic acid treated by magnesium sulfate.

PubMed

Hatch, D M; Atito-Narh, E; Herschmiller, E J; Olufolabi, A J; Owen, M D

2016-05-01

We present a case of accidental injection of tranexamic acid during spinal anesthesia for an elective cesarean delivery. Immediately following intrathecal injection of 2mL of solution, the patient complained of severe back pain, followed by muscle spasm and tetany. As there was no evidence of spinal block, the medications given were checked and a 'used' ampoule of tranexamic acid was found on the spinal tray. General anesthesia was induced but muscle spasm and tetany persisted despite administration of a non-depolarizing muscle relaxant. Hemodynamic instability, ventricular tachycardia, and status epilepticus developed, which were refractory to phenytoin, diazepam, and infusions of thiopental, midazolam and amiodarone. Magnesium sulfate was administered postoperatively in the intensive care unit, following which the frequency of seizures decreased, eventually stopping. Unfortunately, on postoperative day three the patient died from cardiopulmonary arrest after an oxygen supply failure that was not associated with the initial event. This report underlines the importance of double-checking medications before injection in order to avoid a drug error. As well, it suggests that magnesium sulfate may be useful in stopping seizures caused by the intrathecal injection of tranexamic acid. Copyright © 2015 Elsevier Ltd. All rights reserved.

The use of the indicator fluo-5N to measure sarcoplasmic reticulum calcium in single muscle fibres of the cane toad

PubMed Central

Kabbara, Akram A; Allen, David G

2001-01-01

Single fibres from the lumbrical muscles of the cane toad (Bufo marinus) were incubated in fluo-5N AM for 2 h at 35 °C in order to load the indicator into the sarcoplasmic reticulum. Fluo-5N is a low-affinity calcium indicator (KCa 90 μm). Successful sarcoplasmic reticulum (SR) loading was indicated by a fluorescence signal that declined during contraction. Confocal microscopy showed that the dye loaded principally in lines perpendicular to the long axis of the fibre that repeated each sarcomere. This is consistent with much of the dye residing in the SR. To establish the site of loading, fibres were exposed to 30 mm caffeine in the presence of 20 μm 2,5-di(tert-butyl)1,4-hydroquinone (TBQ, an SR pump inhibitor) which should release most Ca2+ from the SR; this procedure reduced the fluorescence to 46 ± 4 % of the control value. To determine how much indicator was in the myoplasm, fibres were exposed to 100 μg ml−1 saponin which permeabilizes the surface membrane; saponin treatment reduced the fluorescence to 51 ± 2 % of the control value. During maximally activated tetani (100 Hz stimulation rate, 22 °C) the component of signal from the SR declined by 33 ± 4 %. During relaxation the SR signal recovered in two phases with time constants of 0.38 ± 0.14 s and 10.1 ± 1.7 s. Partially activated tetani (30 Hz stimulation rate) showed a smaller SR signal. Application of the SR Ca2+ pump inhibitor TBQ slowed the rate of recovery of the SR signal. Muscle fatigue was produced by repeated short tetani until tension was reduced to 50 %. The SR signal during the periods between tetani declined steadily and the SR Ca2+ signal was eventually reduced to 71 ± 8 % of the control signal. This signal recovered in two phases when the muscle was rested. An initial phase had a time constant of 1.7 ± 0.2 s so that by 20 s of recovery the SR Ca2+ signal was 86 ± 7 % of control; the second phase was slower and by 5 min the SR Ca2+ signal was back to control values (98 ± 5 % control). In addition the magnitude of the SR signal decline associated with each tetanus (Δ[Ca2+]SR) declined monotonically throughout fatigue and returned to control after 5 min recovery. This approach can monitor the SR Ca2+ concentration in normally functioning muscle fibres with good time resolution. The method confirms other approaches that show that the free Ca2+ available for release in the SR declines during fatigue. This reduction in [Ca2+]SR will contribute to the failure of Ca2+ delivery to the myofilaments which is an important cause of muscle fatigue. PMID:11432994

The use of the indicator fluo-5N to measure sarcoplasmic reticulum calcium in single muscle fibres of the cane toad.

PubMed

Kabbara, A A; Allen, D G

2001-07-01

1. Single fibres from the lumbrical muscles of the cane toad (Bufo marinus) were incubated in fluo-5N AM for 2 h at 35 degrees C in order to load the indicator into the sarcoplasmic reticulum. Fluo-5N is a low-affinity calcium indicator (K(Ca) 90 microM). Successful sarcoplasmic reticulum (SR) loading was indicated by a fluorescence signal that declined during contraction. 2. Confocal microscopy showed that the dye loaded principally in lines perpendicular to the long axis of the fibre that repeated each sarcomere. This is consistent with much of the dye residing in the SR. 3. To establish the site of loading, fibres were exposed to 30 mM caffeine in the presence of 20 microM 2,5-di(tert-butyl)1,4-hydroquinone (TBQ, an SR pump inhibitor) which should release most Ca(2+) from the SR; this procedure reduced the fluorescence to 46 +/- 4 % of the control value. To determine how much indicator was in the myoplasm, fibres were exposed to 100 microg ml(-1) saponin which permeabilizes the surface membrane; saponin treatment reduced the fluorescence to 51 +/- 2 % of the control value. 4. During maximally activated tetani (100 Hz stimulation rate, 22 degrees C) the component of signal from the SR declined by 33 +/- 4 %. During relaxation the SR signal recovered in two phases with time constants of 0.38 +/- 0.14 s and 10.1 +/- 1.7 s. Partially activated tetani (30 Hz stimulation rate) showed a smaller SR signal. Application of the SR Ca(2+) pump inhibitor TBQ slowed the rate of recovery of the SR signal. 5. Muscle fatigue was produced by repeated short tetani until tension was reduced to 50 %. The SR signal during the periods between tetani declined steadily and the SR Ca(2+) signal was eventually reduced to 71 +/- 8 % of the control signal. This signal recovered in two phases when the muscle was rested. An initial phase had a time constant of 1.7 +/- 0.2 s so that by 20 s of recovery the SR Ca(2+) signal was 86 +/- 7 % of control; the second phase was slower and by 5 min the SR Ca(2+) signal was back to control values (98 +/- 5 % control). In addition the magnitude of the SR signal decline associated with each tetanus (Delta[Ca(2+)](SR)) declined monotonically throughout fatigue and returned to control after 5 min recovery. 6. This approach can monitor the SR Ca(2+) concentration in normally functioning muscle fibres with good time resolution. The method confirms other approaches that show that the free Ca(2+) available for release in the SR declines during fatigue. This reduction in [Ca(2+)](SR) will contribute to the failure of Ca(2+) delivery to the myofilaments which is an important cause of muscle fatigue.

Hypertext and Multimedia for Functional Enhancement of USARIEM Medical Handbooks and Biomedical Simulation Software.

DTIC Science & Technology

1994-12-01

complex Internet addresses. Hypertext and hypermedia documents have logical and physical structure (Shneiderman, 1993). The logical structure delineates...Rubra, Miliaria Profunda , Anhidrotic Heat Exhaustion, Heat Syncope, Heat Edema, Sunburn, and Heat Tetany. The user may return to the main document...military or scientific organizations via digital communications networks such as the Internet . Access clearance would first be obtained from the USARIEM

[Celiac crisis: presentation as bleeding diathesis].

PubMed

Gutiérrez, Sebastián; Toro, Martín; Cassar, Alejandro; Ongay, Rodrigo; Isaguirre, Jorge; López, Candelaria; Benedetti, Laura

2009-03-01

Celiac crisis is a severe and potentially fatal complication of celiac disease. Unusual at present, it has been described mainly in children younger than 2-years-old, but reports in adults do exist. We report a 26-years-old lady with tetany and bleeding diathesis at presentation. In spite of it rareness, it is important to consider celiac crisis among the multiple manifestations of celiac disease.

Distinct Single but Not Necessarily Repeated Tetanization Is Required to Induce Hippocampal Late-LTP in the Rat CA1

ERIC Educational Resources Information Center

Sajikumar, Sreedharan; Navakkode, Sheeja; Frey, Julietta U.

2008-01-01

The protein synthesis-dependent form of hippocampal long-term potentiation (late-LTP) is thought to underlie memory. Its induction requires a distinct stimulation strength, and the common opinion is that only repeated tetani result in late-LTP whereas as single tetanus only reveals a transient early-LTP. Properties of LTP induction were compared…

[Clinical analysis of 6 cases of Bartter syndrome].

PubMed

Yin, Fang-mei; Zheng, Fang-qiu; Zhang, Xin; Wu, Mei-jun; Wei, Hong-yan; Ma, Zhong-shu; Lu, Biao; Qiu, Ming-cai

2011-03-01

To summarize the clinical characteristics of Bartter syndrome and investigate its pathogenesis. The clinical data of 6 cases of Bartter syndrome at our hospital from November 2006 to May 2010 were analyzed retrospectively. The onset age of Bartter syndrome was 13-35 years old. The main symptoms included weakness (6/6), paralysis (1/6), numbness (5/6) and tetany (4/6). All patients had normal blood pressure. The biochemical tests showed persistent hypokalemia, metabolic alkalosis (6/6) and hyperreninemia. The pathological examination of deltoid muscle biopsy showed the swelling, degeneration and necrosis of myocytes and the deposition of immunocomplex in myolemma. And the pathological examination of renal biopsy showed the hyperplasia of juxtaglomerular apparatus (5/6) and the deposition of immunocomplex. All symptoms were relieved after a therapy of potassium supplementation or a combination of indomethacin, spironolactone and immunosuppressant. When such clinical features as weakness, paralysis, tetany, hypokalemic alkalosis and normotension are encountered, Bartter syndrome should be suspected. Serum electrolytes, blood gas analysis and activation of the renin-angiotensin-aldosterone system should be examined for a definite diagnosis. The treatment of choice includes potassium and magnesium supplementation or in combination with prostaglandin synthetase inhibitor, aldosterone antagonist and immunosuppressant. Immunologic mechanism may participate in the course of Bartter syndrome.

A de novo KCNA1 Mutation in a Patient with Tetany and Hypomagnesemia.

PubMed

van der Wijst, Jenny; Konrad, Martin; Verkaart, Sjoerd A J; Tkaczyk, Marcin; Latta, Femke; Altmüller, Janine; Thiele, Holger; Beck, Bodo; Schlingmann, Karl Peter; de Baaij, Jeroen H F

2018-05-23

Mutations in the KCNA1 gene encoding the voltage-gated potassium (K+) channel Kv1.1 have been linked to rare neurological syndromes, episodic ataxia type 1 (EA1) and myokymia. In 2009, a KCNA1 mutation was identified in a large family with autosomal dominant hypomagnesemia. Despite efforts in establishing a genotype-phenotype correlation for the wide variety of symptoms in EA1, little is known on the serum magnesium (Mg2+) levels in these patients. In the present study, we describe a new de novo KCNA1 mutation in a Polish patient with tetany and hypomagnesemia. Electrophysiological and biochemical analyses were performed to determine the pathogenicity of the mutation. A female patient presented with low serum Mg2+ levels, renal Mg2+ wasting, muscle cramps, and tetanic episodes. Whole exome sequencing identified a p.Leu328Val mutation in KCNA1 encoding the Kv1.1 K+ channel. Electrophysiological examinations demonstrated that the p.Leu328Val mutation caused a dominant-negative loss of function of the encoded Kv1.1 channel. Cell surface biotinylation showed normal plasma membrane expression. Taken together, this is the second report linking KCNA1 with hypomagnesemia, thereby emphasizing the need for further evaluation of the clinical phenotypes observed in patients carrying KCNA1 mutations. © 2018 S. Karger AG, Basel.

Generalized Tetanus in a Gyrfalcon ( Falco rusticolus ) with Pododermatitis.

PubMed

Beaufrère, Hugues; Laniesse, Delphine; Stickings, Paul; Tierney, Robert; Sesardic, Thea; Slavic, Durda; Compo, Nicole; Smith, Dale A

2016-12-01

A 2-yr-old male gyrfalcon ( Falco rusticolus ) was presented for severe and generalized muscle spasticity and pododermatitis. The falcon had been treated for pododermatitis over the previous 4 mo. Muscle rigidity and spasms involved the entire bird but were more severe on the right leg. The bird was also tachypneic and hyperthermic at 45 C. While the plantar pododermatitis lesions had healed, there was still a small abscess on the lateral aspect of the right foot. Clinical signs were consistent with tetanus. Several bacteria were isolated from the abscess including Clostridium tetani . The isolate was confirmed to be toxigenic by PCR. Attempts to detect tetanus toxin in the bird's plasma were unsuccessful. The abscess was debrided. The gyrfalcon received equine tetanus antitoxin, intravenous metronidazole, methocarbamol, midazolam, a constant-rate infusion of Fentanyl, active cooling, and supportive care. Inhalant anesthesia with isoflurane was the only treatment that would lower the body temperature and reduce the clinical signs. The gyrfalcon died a few hours after admission. The characteristic clinical signs and isolation of toxigenic C. tetani from a wound were strong supportive evidence for a diagnosis of tetanus. This case constitutes the first reported natural occurrence of tetanus in an avian species. Further information is needed to determine whether gyrfalcons are more susceptible to tetanus than are other avian species and whether pododermatitis lesions may be risk factors.

Human Electro-Muscular Incapacitation (HEMI) Devices Characterization: A Comparative Study on Stress and the Physiological Effects on Swine

DTIC Science & Technology

2011-07-07

depending upon the device. As noted earlier, while the Stinger™S-200 and TASER ® X26 both resulted in tetany (sustained muscle contraction ), the cyclic...artificially maintained by the muscle contraction of the HEMI application. The stoppage of the HEMI “unmasked” the hypovolemia and the blood pressure...dropped. (2) The animals had normal blood volume with peripheral vascular resistance maintained by the HEMI ( muscle contraction ). When the HEMI

Hyperparathyroid crisis presenting with hyperemesis gravidarum.

PubMed

Yilmaz, Banu Aktaş; Altay, Mustafa; Değertekin, Ceyla Konca; Çimen, Ali Riza; Iyidir, Özlem Turhan; Biri, Aydan; Yüksel, Osman; Törüner, Füsun Baloş; Arslan, Metin

2014-10-01

Primary hyperparathyroidism during pregnancy is a rare condition, and the diagnosis may be confounded by pregnancy related conditions. Since the appropriate management reduces the maternal and fetal complications; differential diagnosis becomes quite crucial. Clinical course of a patient with hyperparathyroid crisis will be discussed with the review of the literature. A 22-year- old, (gravida 2, para 1) woman was presented with hyperparathyroid crisis at the 11th weeks' gestation. She was hospitalized twice due to hyperemesis gravidarum. When she was admitted to the hospital for the third time due to increased vomiting and weight-loss, serum biochemistry panel was performed and it revealed severe hypercalcemia that serum Ca was 17.59 mg/dl, and she was referred to our hospital as parathyroid crisis. Maternal hypercalcemia was resolved after urgent parathyroidectomy. She was diagnosed as preeclampsia at the 30 weeks' gestation and delivered a male infant weighing 1,090 g at 33 weeks' gestation with APGAR scores 6 at 1 min, and 7 at min 5, without evidence of neonatal hypocalcemia or tetany. Urgent parathyroidectomy is the definite treatment in symptomatic patients with hyperparathyroidism during pregnancy. Resolving maternal hypercalcemia prevents neonatal tetany and hypocalcemia. Hyperemesis may lead to hypercalcemic crisis in patients with hyperparathyroidism, so serum Ca level should be checked in patients with hyperemesis gravidarum especially who detoriate rapidly. Although they share some common pathogenetic mechanisms, there is not enough evidence for attributing preeclampsia to primary hyperparathyroidism.

Interpolated twitches in fatiguing single mouse muscle fibres: implications for the assessment of central fatigue

PubMed Central

Place, Nicolas; Yamada, Takashi; Bruton, Joseph D; Westerblad, Håkan

2008-01-01

An electrically evoked twitch during a maximal voluntary contraction (twitch interpolation) is frequently used to assess central fatigue. In this study we used intact single muscle fibres to determine if intramuscular mechanisms could affect the force increase with the twitch interpolation technique. Intact single fibres from flexor digitorum brevis of NMRI mice were dissected and mounted in a chamber equipped with a force transducer. Free myoplasmic [Ca2+] ([Ca2+]i) was measured with the fluorescent Ca2+ indicator indo-1. Seven fibres were fatigued with repeated 70 Hz tetani until 40% initial force with an interpolated pulse evoked every fifth tetanus. Results showed that the force generated by the interpolated twitch increased throughout fatigue, being 9 ± 1% of tetanic force at the start and 19 ± 1% at the end (P < 0.001). This was not due to a larger increase in [Ca2+]i induced by the interpolated twitch during fatigue but rather to the fact that the force–[Ca2+]i relationship is sigmoidal and fibres entered a steeper part of the relationship during fatigue. In another set of experiments, we observed that repeated tetani evoked at 150 Hz resulted in more rapid fatigue development than at 70 Hz and there was a decrease in force (‘sag’) during contractions, which was not observed at 70 Hz. In conclusion, the extent of central fatigue is difficult to assess and it may be overestimated when using the twitch interpolation technique. PMID:18403421

Steroid-induced hypocalcaemia with tetany in a patient with hypoparathyroidism.

PubMed

Oikonomou, Dimitrios; Laina, Ageliki; Xydaki, Aikaterini; Christopoulos, Constantinos

2014-11-18

Although glucocorticoids have a known negative effect on calcium balance, they do not normally cause clinically significant hypocalcaemia. A young woman with post-surgical hypoparathyroidism developed symptomatic hypocalcaemia on two occasions following treatment with intravenous hydrocortisone for allergic reactions. Oral calcium and vitamin D supplementation could not prevent the development of hypocalcaemia. She was treated successfully with intravenous calcium gluconate infusions and discontinuation of glucocorticoids. In patients with hypoparathyroidism, impaired parathyroid hormone response to steroid-induced negative calcium balance may result in severe symptomatic hypocalcaemia requiring hospitalisation. 2014 BMJ Publishing Group Ltd.

Steroid-induced hypocalcaemia with tetany in a patient with hypoparathyroidism

PubMed Central

Oikonomou, Dimitrios; Laina, Ageliki; Xydaki, Aikaterini; Christopoulos, Constantinos

2014-01-01

Although glucocorticoids have a known negative effect on calcium balance, they do not normally cause clinically significant hypocalcaemia. A young woman with post-surgical hypoparathyroidism developed symptomatic hypocalcaemia on two occasions following treatment with intravenous hydrocortisone for allergic reactions. Oral calcium and vitamin D supplementation could not prevent the development of hypocalcaemia. She was treated successfully with intravenous calcium gluconate infusions and discontinuation of glucocorticoids. In patients with hypoparathyroidism, impaired parathyroid hormone response to steroid-induced negative calcium balance may result in severe symptomatic hypocalcaemia requiring hospitalisation. PMID:25406219

CHANGES IN THE PERCENTAGE OF CALCIUM AND PHOSPHORUS OF THE BLOOD FOLLOWING SECTION OF THE SYMPATHETIC AND VAGUS NERVES

PubMed Central

Berg, Benjamin N.; Hess, Alfred F.; Sherman, Elizabeth

1928-01-01

When a splanchnic nerve or the celiac plexus was severed a definite fall in serum calcium resulted, the level falling to 6 mg. per cent and remaining low for 1 or 2 weeks. Tetany, however, did not develop. The inorganic phosphate was slightly altered. On the other hand, when the vagi nerves were severed, the serum calcium rose. The equilibrium of both calcium and phosphorus was rendered less stable by the division of the sympathetic or the parasympathetic nerves. PMID:19869390

Severe Hypocalcemia in a Patient with Recurrent Chondrosarcoma.

PubMed

Eun, Jung Nam; Choi, Yoo Duk; Lee, Jeong Ho; Jeong, Yun Ah; Yoon, Jee Hee; Kim, Hee Kyung; Kang, Ho-Cheol

2017-01-01

Hypocalcemia is relatively uncommon paraneoplastic syndrome. Only one case of hypocalcemia has been reported in a patient with chondrosarcoma. We herein report a case of a 32-year-old woman with metastatic chondrosarcoma with tetany. Her imaging findings revealed multiple calcific metastatic lesions in the lungs, pancreas, left atrium, and pulmonary vein. A laboratory examination showed hypocalcemia with no evidence of any other disease that could induce hypocalcemia. On the basis of the laboratory and clinical findings, we concluded the etiology of her severe hypocalcemia to be excessive calcium consumption by the tumor itself.

Cephalic Tetanus in an Immunized Teenager: An Unusual Case Report.

PubMed

Felter, Robert A; Zinns, Lauren E

2015-07-01

Tetanus is a rare disease in developed countries but is prevalent worldwide. It has significant morbidity and mortality. The causative agent Clostridium tetani is ubiquitous in nature. In the United States, approximately 50 to 100 cases are reported per year but rarely in immunocompetent, fully immunized patients. Of the four types of tetanus (generalized, neonatal, cephalic, and localized), cephalic is the least common. We present a case of cephalic tetanus in a 14-year-old boy who completed his primary immunizations with a video of his physical examination findings.

Disinfection methods for spores of Bacillus atrophaeus, B. anthracis, Clostridium tetani, C. botulinum and C. difficile.

PubMed

Oie, Shigeharu; Obayashi, Akiko; Yamasaki, Hirofumi; Furukawa, Hiroyuki; Kenri, Tsuyoshi; Takahashi, Motohide; Kawamoto, Keiko; Makino, Sou-ichi

2011-01-01

To evaluate disinfection methods for environments contaminated with bioterrorism-associated microorganism (Bacillus anthracis), we performed the following experiments. First, the sporicidal effects of sodium hypochlorite on spores of five bacterial species were evaluated. Bacillus atrophaeus was the most resistant to hypochlorite, followed in order by B. anthracis, Clostridium botulinum and Clostridium tetani, and Clostridium difficile. Subsequently, using B. atrophaeus spores that were the most resistant to hypochlorite, the sporicidal effects of hypochlorite at lower pH by adding vinegar were evaluated. Hypochlorite containing vinegar had far more marked sporicidal effects than hypochlorite alone. Cleaning with 0.5% (5000 ppm) hypochlorite containing vinegar inactivated B. atrophaeus spores attached to vinyl chloride and plywood plates within 15 s, while that not containing vinegar did not inactivate spores attached to cement or plywood plates even after 1 h. Therefore, the surfaces of cement or plywood plates were covered with gauze soaked in 0.5% hypochlorite containing vinegar, and the sporicidal effects were evaluated. B. atrophaeus spores attached to plywood plates were not inactivated even after 6 h, but those attached to cement plates were inactivated within 5 min. On the other hand, covering the surfaces of plywood plates with gauze soaked in 0.3% peracetic acid and gauze soaked in 2% glutaral inactivated B. atrophaeus spores within 5 min and 6 h, respectively. These results suggest that hypochlorite containing vinegar is effective for disinfecting vinyl chloride, tile, and cement plates contaminated with B. anthracis, and peracetic acid is effective for disinfecting plywood plates contaminated with such microorganism.

Technetium-99m Pyrophosphate: Comparison of ED50 for Tetany and Acidosis with Acute LD500

DTIC Science & Technology

electrocardiogram and chemical analysis revealed that the hypocalcemic effect occurs at a much lower dosage than for the LD50. Polyphosphate was found to be more...toxic by the LD50 analysis than pyrophosphate. It is emphasized that the hypocalcemic toxic effects should be the determining factor in deciding what...to 1 with regard to the first signs of hypocalcemia by electrocardiographic measurements (i.e., 2 mg/kg). On this basis an injection of no more than 1 mg/kg is recommended to maintain a safety factor of around 10 to 1.

Hypocalcemia-Induced Seizure

PubMed Central

Trinidad, Bradley J.; Shi, Jiong

2015-01-01

Calcium is essential for both neurotransmitter release and muscle contraction. Given these important physiological processes, it seems reasonable to assume that hypocalcemia may lead to reduced neuromuscular excitability. Counterintuitively, however, clinical observation has frequently documented hypocalcemia’s role in induction of seizures and general excitability processes such as tetany, Chvostek’s sign, and bronchospasm. The mechanism of this calcium paradox remains elusive, and very few pathophysiological studies have addressed this conundrum. Nevertheless, several studies primarily addressing other biophysical issues have provided some clues. In this review, we analyze the data of these studies and propose an integrative model to explain this hypocalcemic paradox. PMID:25810356

Severe Hypocalcemia in a Patient with Recurrent Chondrosarcoma

PubMed Central

Eun, Jung Nam; Choi, Yoo Duk; Lee, Jeong Ho; Jeong, Yun Ah; Yoon, Jee Hee; Kim, Hee Kyung; Kang, Ho-Cheol

2017-01-01

Hypocalcemia is relatively uncommon paraneoplastic syndrome. Only one case of hypocalcemia has been reported in a patient with chondrosarcoma. We herein report a case of a 32-year-old woman with metastatic chondrosarcoma with tetany. Her imaging findings revealed multiple calcific metastatic lesions in the lungs, pancreas, left atrium, and pulmonary vein. A laboratory examination showed hypocalcemia with no evidence of any other disease that could induce hypocalcemia. On the basis of the laboratory and clinical findings, we concluded the etiology of her severe hypocalcemia to be excessive calcium consumption by the tumor itself. PMID:28717079

Gitelman's Syndrome Presenting with Hypocalcaemia - A Case Report.

PubMed

Cader, F A; Kabir, A; Mayedah, R; Masud, M S; Quadir, F; Hossen, M N

2015-04-01

Gitelman's syndrome is an autosomal recessive renal tubular disorder characterized by severe hypomagnesaemia, hypokalaemia, metabolic alkalosis and hypocalcaemia. It is caused by defective NaCl transport in the Distal Convoluted Tubule and presents in adolescence or adulthood, with a distinctly more benign course than Bartter's Syndrome. The dominant clinical features are muscle weakness, fatigue, carpopedal spasm, cramps and tetany. We report the case of a 26 year old male who presented with flaccid quadriparesis and carpopedal spasms, hypokalaemia, hypomagnesaemia, hypocalcaemia and severe urinary magnesium wasting. He was treated with potassium and magnesium supplementation and regained full function of all limbs.

Magnesium, stress and neuropsychiatric disorders.

PubMed

Galland, L

Magnesium has a profound effect on neural excitability; the most characteristic signs and symptoms of Mg deficiency are produced by neural and neuromuscular hyperexcitability. These create a constellation of clinical findings termed tetany syndrome (TS). TS symptoms include muscle spasms, cramps and hyperarousal, hyperventilation and asthenia. Physical signs (Chvostek's, Trousseau's or von Bonsdorff's) and abnormalities of the electromyogram or electroencephalogram can usually be elicited. Signs and symptoms of TS are frequently encountered in clinical practice, especially among patients with functional or stress-related disorders. The role of Mg deficit in TS is suggested by relatively low levels of serum or erythrocyte Mg and by the clinical response to oral Mg salts, which has been demonstrated in controlled studies. Among the more serious neurologic sequelae of TS are migraine attacks, transient ischemic attacks, sensorineural hearing loss and convulsions. Mg deficiency may predispose to hyperventilation and may sensitize the cerebral vasculature to the effects of hypocarbia. Mg deficiency increases susceptibility to the physiologic damage produced by stress, and Mg administration has a protective effect; studies on noise stress and noise-induced hearing loss are taken as an example. In addition, the adrenergic effects of psychological stress induce a shift of Mg from the intracellular to the extracellular space, increasing urinary excretion and eventually depleting body stores. Drugs used in neurology and psychiatry may affect Mg levels in blood and may diminish signs of tetany, making assessment of Mg status more difficult. Pharmacologic use of Mg can decrease neurologic deficit in experimental head trauma, possibly by blockade of N-methyl-D-aspartate receptors. In conjunction with high doses of pyridoxine, Mg salts benefit 40% of patients with autism, possibly by an effect on dopamine metabolism.

Increasing Incidence of Nutritional Rickets: A Population-Based Study in Olmsted County, Minnesota

PubMed Central

Thacher, Tom D.; Fischer, Philip R.; Tebben, Peter J.; Singh, Ravinder J.; Cha, Stephen S.; Maxson, Julie A.; Yawn, Barbara P.

2013-01-01

Objective To determine temporal trends in incidence and risk factors of nutritional rickets in a community-based population. Patients and Methods Rochester Epidemiology Project (REP) data were used to identify all children (<18 years) residing in Olmsted County, Minnesota between January 1, 1970 and December 31, 2009 with diagnostic codes corresponding to rickets, vitamin D deficiency, hypovitaminosis D, rachitis, osteomalacia, genu varum, genu valgum, craniotabes, hypocalcemia, hypocalcemic seizure, and tetany. Record abstraction was performed to select subjects with radiographic confirmation of rickets. Age- and gender-matched controls were identified for evaluation of risk factors. The main outcome measure was radiographic rickets without identifiable inherited, genetic, or non-nutritional causes. Incidence rates were calculated using REP census data. Results Of 768 children with eligible diagnostic codes, 23 had radiographic evidence of rickets; of these, 17 children had nutritional rickets. All were younger than 3 years and 13 (76%) were nonwhite. Clinical presentation included poor growth (n=12), leg deformity (n=8), motor delay (n=5), leg pain (n=3), weakness (n=3), and hypocalcemia or tetany (n=2). The incidence of nutritional rickets in children under 3 years was 0, 2.2, 3.7, and 24.1 per 100,000 for the decades beginning in 1970, 1980, 1990, and 2000, respectively (P=.003 for incidence trend). Nutritional rickets was associated with black race, breastfeeding, low birth weight, and stunted growth (P<.05 for all). Four of 13 (31%) who underwent 25-hydroxyvitamin D testing had values less than 10 ng/mL (25 nmol/L). Conclusion Nutritional rickets remains rare, but the incidence has dramatically increased after 2000. Not all cases can be attributed to vitamin D deficiency. PMID:23374621

Tetany caused by chronic diarrhea in a child with celiac disease: A case report

PubMed Central

Hurtado-Valenzuela, Jaime Gabriel; Sotelo-Cruz, Norberto; López-Cervantes, Guillermo; de la Barca, Ana María Calderón

2008-01-01

There is no awareness about celiac disease (CD) in Mexico. A 2.9 year old mestizo boy was admitted to a Mexican hospital with muscle cramps and fine tremors. He suffered chronic diarrhea, abdominal distention, hypotrophic limbs, stunting and wasting, and presented hypocalcemia, anemia and high titers of serological markers. Diagnosis of CD was confirmed by a duodenal biopsy. After replacement of calcium and a gluten-free diet, the symptoms resolved within 6 weeks. After 2-months, serum analyses, anthropometric data as well as antibodies titers were normal after 4 years. CD screening tests are needed in chronic diarrhea for any ethnicity patients. PMID:18811963

Endocrine causes of calcium disorders.

PubMed

Greco, Deborah S

2012-11-01

Endocrine diseases that may cause hypercalcemia and hypocalcemia include hyperparathyroidism, hypoparathyroidism, thyroid disorders, hyperadrenocorticism, hypoadrenocorticism, and less commonly pheochromocytoma and multiple endocrine neoplasias. The differential diagnosis of hypercalcemia may include malignancy (lymphoma, anal sac carcinoma, and squamous cell carcinoma), hyperparathyroidism, vitamin D intoxication, chronic renal disease, hypoadrenocorticism, granulomatous disorders, osteolysis, or spurious causes. Hypocalcemia may be caused by puerperal tetany, pancreatitis, intestinal malabsorption, ethlyene glycol intoxication, acute renal failure, hypopararthyroidism, hypovitaminosis D, hypomagnesemia, and low albumin. This article focuses on the endocrine causes of calcium imbalance and provides diagnostic and therapeutic guidelines for identifying the cause of hypercalcemia and hypocalcemia in veterinary patients. Copyright © 2012 Elsevier Inc. All rights reserved.

Free radicals in tetanic activity of isolated skeletal muscle.

PubMed

Koren, A; Sauber, C; Sentjurc, M; Schara, M

1983-01-01

1. The concentration of the free radicals in muscle tissue mitochondria changes with the phase of muscle contraction. 2. Potassium cyanide (KCN) influences the shape of the isotonic tetani mechanograms; the contraction is still strong and qualitatively comparable in amplitude to untreated controls. 3. On the other hand, the correlation between the free radical concentration and muscle contraction is lost. 4. The free radical concentration in isolated mitochondria is influenced by KCN and potassium ferricyanide. 5. The free radical concentration changes due to the electron flow in the respiratory chain. 6. Inhibition of the respiratory phosphorylation by KCN could affect the free radical level.

Extreme hyperphosphatemia and hypocalcemic coma associated with phosphate enema.

PubMed

Hsu, Heng Jung; Wu, Mai-Szu

2008-01-01

Fleet enema (sodium phosphate, C.B. Fleet Co., Inc., Lynchburg, Virginia) is widely used for bowel preparation or constipation relief in the hospital and over the counter. The potential risks, including hyperphosphatemia and hypocalcemic coma should be kept in mind of primary care physician. The patients with older age, bowel obstruction, small intestinal disorders, poor gut motility, and renal disease are contraindicated or should be administered with caution. We present a patient with old age and chronic renal failure who developed severe hyperphosphatemia and hypocalcemic tetany with coma after sodium phosphate enema. We recommend the use of alternative enema preparations, such as simple tap water or saline solution enemas, which can prevent fatal complications in high risk patients.

Tetanus toxoid vaccine: Elimination of neonatal tetanus in selected states of India

PubMed Central

Verma, Ramesh; Khanna, Pardeep

2012-01-01

Tetanus is caused by a neurotoxin produced by Clostridium tetani (C. tetani), a spore-forming bacterium. Infection begins when tetanus spores are introduced into damaged tissue. Tetanus is characterized by muscle rigidity and painful muscle spasms caused by tetanus toxin’s blockade of inhibitory neurons that normally oppose and modulate the action of excitatory motor neurons. Maternal and neonatal tetanus (MNT) are caused by unhygienic methods of delivery, abortion, or umbilical-cord care. Maternal and neonatal tetanus are both forms of generalized tetanus and have similar clinical courses. About 90% of neonates with tetanus develop symptoms in the first 3–14 d of life, mostly on days 6–8, distinguishing neonatal tetanus from other causes of neonatal mortality which typically occur during the first two days of life. Overall case fatality rates for patients admitted to the hospital with neonatal tetanus in developing countries are 8–50%, while the fatality rate can be as high as 100% without hospital care. Tetanus toxoid (TT) vaccination of pregnant women to prevent neonatal tetanus was included in WHO’s Expanded Program on Immunization (EPI) a few years after its inception in 1974. In 2000, WHO, UNICEF, and UNFPA formed a partnership to relaunch efforts toward this goal, adding the elimination of maternal tetanus as a program objective, and setting a new target date of 2005. By February 2007, 40 countries had implemented tetanus vaccination campaigns in high-risk areas, targeting more than 94 million women, and protecting more than 70 million subjects with at least two doses of TT. In 2011, 653 NT cases were reported in India compared with 9313 in 1990. As of February 2012, 25 countries and 15 States and Union Territories of India, all of Ethiopia except Somaliland, and almost 29 of 34 provinces in Indonesia have been validated to have eliminated MNT. PMID:22894950

Tetanus toxoid vaccine: elimination of neonatal tetanus in selected states of India.

PubMed

Verma, Ramesh; Khanna, Pardeep

2012-10-01

Tetanus is caused by a neurotoxin produced by Clostridium tetani (C. tetani), a spore-forming bacterium. Infection begins when tetanus spores are introduced into damaged tissue. Tetanus is characterized by muscle rigidity and painful muscle spasms caused by tetanus toxin's blockade of inhibitory neurons that normally oppose and modulate the action of excitatory motor neurons. Maternal and neonatal tetanus (MNT) are caused by unhygienic methods of delivery, abortion, or umbilical-cord care. Maternal and neonatal tetanus are both forms of generalized tetanus and have similar clinical courses. About 90% of neonates with tetanus develop symptoms in the first 3-14 d of life, mostly on days 6-8, distinguishing neonatal tetanus from other causes of neonatal mortality which typically occur during the first two days of life. Overall case fatality rates for patients admitted to the hospital with neonatal tetanus in developing countries are 8-50%, while the fatality rate can be as high as 100% without hospital care. Tetanus toxoid (TT) vaccination of pregnant women to prevent neonatal tetanus was included in WHO's Expanded Program on Immunization (EPI) a few years after its inception in 1974. In 2000, WHO, UNICEF, and UNFPA formed a partnership to relaunch efforts toward this goal, adding the elimination of maternal tetanus as a program objective, and setting a new target date of 2005. By February 2007, 40 countries had implemented tetanus vaccination campaigns in high-risk areas, targeting more than 94 million women, and protecting more than 70 million subjects with at least two doses of TT. In 2011, 653 NT cases were reported in India compared with 9313 in 1990. As of February 2012, 25 countries and 15 States and Union Territories of India, all of Ethiopia except Somaliland, and almost 29 of 34 provinces in Indonesia have been validated to have eliminated MNT.

Increasing incidence of nutritional rickets: a population-based study in Olmsted County, Minnesota.

PubMed

Thacher, Tom D; Fischer, Philip R; Tebben, Peter J; Singh, Ravinder J; Cha, Stephen S; Maxson, Julie A; Yawn, Barbara P

2013-02-01

To determine temporal trends in incidence and risk factors of nutritional rickets in a community-based population. Rochester Epidemiology Project data were used to identify all children (aged <18 years) residing in Olmsted County, Minnesota, between January 1, 1970, and December 31, 2009, with diagnostic codes corresponding to rickets, vitamin D deficiency, hypovitaminosis D, rachitis, osteomalacia, genu varum, genu valgum, craniotabes, hypocalcemia, hypocalcemic seizure, and tetany. Record abstraction was performed to select individuals with radiographic confirmation of rickets. Age- and sex-matched controls were identified for the evaluation of risk factors. The main outcome measure was radiographic evidence of rickets without identifiable inherited, genetic, or nonnutritional causes. Incidence rates were calculated using Rochester Epidemiology Project census data. Of 768 children with eligible diagnostic codes, 23 had radiographic evidence of rickets; of these, 17 children had nutritional rickets. All 17 children were younger than 3 years, and 13 (76%) were of nonwhite race/ethnicity. Clinical presentation included poor growth (n=12), leg deformity (n=8), motor delay (n=5), leg pain (n=3), weakness (n=3), and hypocalcemia or tetany (n=2). The incidence of nutritional rickets in children younger than 3 years was 0, 2.2, 3.7, and 24.1 per 100,000 for the decades beginning in 1970, 1980, 1990, and 2000, respectively (P=.003 for incidence trend). Nutritional rickets was associated with black race, breast-feeding, low birth weight, and stunted growth (P<.05 for all). Four of 13 patients (31%) who underwent 25-hydroxyvitamin D testing had values less than 10 ng/mL. Nutritional rickets remains rare, but its incidence has dramatically increased since 2000. Not all cases of rickets can be attributed to vitamin D deficiency. Copyright © 2013 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Eradication of tetanus.

PubMed

Thwaites, C L; Loan, H T

2015-01-01

The causative agent of tetanus, Clostridium tetani is widespread in the environment throughout the world and cannot be eradicated. To reduce the number of cases of tetanus efforts are focussed on prevention using vaccination and post-exposure wound care. Medline, Pubmed and Cochrane databases; World Health Organization and United Nations Children's Fund publications. The maternal and neonatal tetanus elimination initiative has resulted in significant reductions in mortality from neonatal tetanus throughout the world. Although there are few data available it is likely that large numbers of children and adults, particularly men, remain unprotected due to lack of booster immunization. It remains unclear how HIV and malaria affect both responses to vaccination and transplacental transfer of antibodies or how this might affect timing of vaccination doses. © The Author 2015. Published by Oxford University Press.

Human soil-borne pathogens and risks associated with land use change

NASA Astrophysics Data System (ADS)

Pereg, Lily

2017-04-01

Soil is a source of pathogenic, neutral and beneficial microorganisms. Natural events and anthropogenic activity can affect soil biodiversity and influence the balance and distribution of soil-borne human pathogens. Important bacterial and fungal pathogens, such as Bacillus anthracis, Coxiella bernetii, Clostridium tetani, Escherichia coli 0157:H7, Listeria monocytogenes, Aspergillus fumigatus and Sporothrix schenckii will be discussed. This presentation will concentrate on soil pathogenic microorganisms and the effects of land use change on their prevalence and distribution. In particular, the potential of agricultural soil cultivation to enhance pathogen transmission to human through the release of soil microbes into the air attached to dust particles, contamination of waterways and infection of food plants and animal. Emerging solutions, such as biocontrol and probiotics, will be discussed.

Eradication of tetanus

PubMed Central

Thwaites, C. L.; Loan, H. T.

2015-01-01

Introduction The causative agent of tetanus, Clostridium tetani is widespread in the environment throughout the world and cannot be eradicated. To reduce the number of cases of tetanus efforts are focussed on prevention using vaccination and post-exposure wound care. Sources of data Medline, Pubmed and Cochrane databases; World Health Organization and United Nations Children's Fund publications. Areas of agreement The maternal and neonatal tetanus elimination initiative has resulted in significant reductions in mortality from neonatal tetanus throughout the world. Areas of controversy Although there are few data available it is likely that large numbers of children and adults, particularly men, remain unprotected due to lack of booster immunization. Areas timely for developing research It remains unclear how HIV and malaria affect both responses to vaccination and transplacental transfer of antibodies or how this might affect timing of vaccination doses. PMID:26598719

Hyperventilation of pregnancy presenting with flaccid quadriparesis due to hypokalaemia secondary to respiratory alkalosis.

PubMed

Santra, Gouranga; Paul, Rudrajit; Das, Shubhabrata; Pradhan, Sourav

2014-06-01

Hyperventilation in pregnancy is a cause of chronic respiratory alkalosis. Alkalosis either metabolic or respiratory may cause intracellular shift of potassium ions that may lead to hypokalaemia. However, the resultant hypokalaemia in respiratory alkalosis is usually mild and does not cause much clinical features. A five-months-pregnant female of the age 25 years presented with sudden onset flaccid weakness of both lower limbs associated with thigh muscle pain followed by weakness of both upper limbs within three days. Subsequent investigation revealed severe hypokalaemia due to acute exacerbation of chronic respiratory alkalosis secondary to hyperventilation of pregnancy, other causes of hypokalaemia being ruled out. Respiratory alkalosis causes tetany and other clinical manifestations. But hypokalaemia and such weakness is rarely found. Thisis probably the first report of this type from India.

Pseudohypoparathyroidism type 1B - a rare cause of tetany: case report.

PubMed

Garcia, Catarina; Correia, Cátia R; Lopes, Lurdes

2017-06-26

Pseudohypoparathyroidism (PHP) is a rare group of disorders characterised by end-organ resistance to the parathyroid hormone (PTH). A 16-year-old boy presented with a 2-year history of involuntary dystonic movements involving mainly the left hand, initially after writing and later during physical exercise. Serum calcium was 1.37 mmol/L (2.20-2.69), phosphate 2.1 mmol/L (0.8-1.45) and PTH 302 ng/L (12-88). CT scan of the head demonstrated multiple subcortical and diffuse basal ganglia calcifications. Genetic analysis confirmed a methylation defect in the GNAS cluster on chromosome 20q13.32 which established the diagnosis. Treatment with calcitriol and calcium carbonate led to complete remission of symptoms. Causes of hypocalcaemia should be considered in evaluating patients with movement disorders. The diagnosis of PHP-1B is challenging but the overall prognosis is excellent.

Carrot cells: a pioneering platform for biopharmaceuticals production.

PubMed

Rosales-Mendoza, Sergio; Tello-Olea, Marlene Anahí

2015-03-01

Carrot (Daucus carota L.) is of importance in the molecular farming field as it constitutes the first plant species approved to produce biopharmaceuticals for human use. In this review, features that make carrot an advantageous species in the molecular farming field are analyzed and a description of the developments achieved with this crop thus far is presented. A guide for genetic transformation procedures is also included. The state of the art comprises ten vaccine prototypes against Measles virus, Hepatitis B virus, Human immunodeficiency virus, Yersinia pestis, Chlamydia trachomatis, Mycobacterium tuberculosis, enterotoxigenic Escherichia coli, Corynebacterium diphtheria/Clostridium tetani/Bordetella pertussis, and Helicobacter pylori; as well as the case of the glucocerebrosidase, an enzyme used for replacement therapy, and other therapeutics. Perspectives for these developments are envisioned and innovations are proposed such as the use of transplastomic technologies-, hairy roots-, and viral expression-based systems to improve yields and develop new products derived from this advantageous plant species.

Symmetrical and bilateral basal ganglia calcification. Case series and literature review.

PubMed

Jiménez-Ruiz, Amado; Cárdenas-Sáenz, Omar; Ruiz-Sandoval, José Luis

2018-01-01

Symmetric, bilateral basal ganglia calcification is rare finding that sometimes occurs asymptomatically. Its prevalence increases with age, and the most affected site is the globus pallidus. A series of seven cases with clinical and imaging diagnosis of basal ganglia calcification, recorded during the 2012 to 2016 period at the Department of Internal Medicine of the Hospital Civil de Guadalajara "Fray Antonio Alcalde, is presented. Most common clinical presentation was with altered alertness, headache and seizures. There was one case with movement disorders; there were no cases identified with dementia or tetany. Ganglia calcification can be associated with age-related neurodegenerative changes, but it can be an initial manifestation of a variety of systemic pathologies, including disorders of the calcium metabolism, intoxication by different agents, and autoimmune and genetic diseases. Correlation of typical imaging findings with clinical manifestations and laboratory results should be established to reach a definitive judgment. Copyright: © 2018 SecretarÍa de Salud.

India is on the way forward to maternal and neonatal tetanus elimination!

PubMed Central

Bairwa, Mohan; S.K., Shashikantha; Rajput, Meena; Khanna, Pardeep; Malik, Jagbir Singh; Nagar, Mukesh

2012-01-01

Tetanus is an acute, potentially fatal disease, caused by a bacterium, Clostridium tetani. The disease usually occurs in newborns through infection of the unhealed umbilical stump, particularly when the stump is cut with a non-sterile instrument. NT contributes to 5–7% of neonatal mortality worldwide. Several thousand mothers are also estimated to die annually of maternal tetanus. MNT elimination relies on promotion of maternal tetanus immunization along with safe delivery and avoidance of unsafe abortion and umbilical cord care practices. The Government of India (1983) introduced at least two doses of tetanus toxoid vaccine (TT) to all pregnant women during each pregnancy as a part of its nationwide immunization policy. To date, a total of 15 States including union territories of the India have achieved NT elimination. The remaining Indian States need to strengthen TT coverage to save the lives of neonates as well as mothers from tetanus. PMID:22854674

Beneficial and harmful roles of bacteria from the Clostridium genus.

PubMed

Samul, Dorota; Worsztynowicz, Paulina; Leja, Katarzyna; Grajek, Włodzimierz

2013-01-01

Bacteria of the Clostridium genus are often described only as a biological threat and a foe of mankind. However, many of them have positive properties and thanks to them they may be used in many industry branches (e.g., in solvents and alcohol production, in medicine, and also in esthetic cosmetology). During the last 10 years interest in application of C. botulinum and C. tetani in medicine significantly increased. Currently, the structure and biochemical properties of neurotoxins produced by these bacterial species, as well as possibilities of application of such toxins as botulinum as a therapeutic factor in humans, are being intensely researched. The main aim of this article is to demonstrate that bacteria from Clostridium spp. are not only pathogens and the enemy of humanity but they also have many important beneficial properties which make them usable among many chemical, medical, and cosmetic applications.

Factors Modulating Recovery Rate after Intermittent Tetanic Fatigue in Atrophic Soleus

NASA Astrophysics Data System (ADS)

Li, Hui; Jiao, Bo; Yu, Zhibin

2008-06-01

To specify the factors modulating the recovery rate after intermittent tetanic fatigue in soleus, and to seek the reasons for the decrease of recovery rate in atrophic soleus, we observed the recovery time course of different types of fatigue in isolated muscle strips. A 10 % or 50 % decrease in maximal contraction tension of tetani was defined respectively as slight or moderate fatigue. Tetanic tension recovery rates after short-term and long-term of slight or moderate fatigue were observed, some pharmacological intervention were also used. The results showed that slight fatigue only induced an inhibition to myofibril, while moderate fatigue induced an inhibition in myofibril and sarcoplasmic reticulum Ca2+ release channels. There were significant decreases in all of the fatigue groups in one-week tail-suspended rats. These suggest that both slight and moderate fatigue inhibit the myofibrils and the sarcoplasmic reticulum Ca2+ release channels in one-week unloaded soleus.

India is on the way forward to maternal and neonatal tetanus elimination!

PubMed

Bairwa, Mohan; Sk, Shashikantha; Rajput, Meena; Khanna, Pardeep; Malik, Jagbir Singh; Nagar, Mukesh

2012-08-01

Tetanus is an acute, potentially fatal disease, caused by a bacterium, Clostridium tetani. The disease usually occurs in newborns through infection of the unhealed umbilical stump, particularly when the stump is cut with a non-sterile instrument. NT contributes to 5-7% of neonatal mortality worldwide. Several thousand mothers are also estimated to die annually of maternal tetanus. MNT elimination relies on promotion of maternal tetanus immunization along with safe delivery and avoidance of unsafe abortion and umbilical cord care practices. The Government of India (1983) introduced at least two doses of tetanus toxoid vaccine (TT) to all pregnant women during each pregnancy as a part of its nationwide immunization policy. To date, a total of 15 States including union territories of the India have achieved NT elimination. The remaining Indian States need to strengthen TT coverage to save the lives of neonates as well as mothers from tetanus.

Everolimus for Primary Intestinal Lymphangiectasia With Protein-Losing Enteropathy.

PubMed

Ozeki, Michio; Hori, Tomohiro; Kanda, Kaori; Kawamoto, Norio; Ibuka, Takashi; Miyazaki, Tatsuhiko; Fukao, Toshiyuki

2016-03-01

Primary intestinal lymphangiectasia (PIL), also known as Waldmann's disease, is an exudative enteropathy resulting from morphologic abnormalities in the intestinal lymphatics. In this article, we describe a 12-year-old boy with PIL that led to protein-losing enteropathy characterized by diarrhea, hypoalbuminemia associated with edema (serum albumin level: 1.0 g/dL), and hypogammaglobulinemia (serum IgG level: 144 mg/dL). Severe hypoalbuminemia, electrolyte abnormalities, and tetany persisted despite a low-fat diet and propranolol. Everolimus (1.6 mg/m(2)/day) was added to his treatment as an antiangiogenic agent. With everolimus treatment, the patient's diarrhea resolved and replacement therapy for hypoproteinemia was less frequent. Hematologic and scintigraphy findings also improved (serum albumin level: 2.5 g/dL). There were no adverse reactions during the 12-month follow-up. To the best of our knowledge, this is the first report of everolimus use in a patient with PIL. Copyright © 2016 by the American Academy of Pediatrics.

Nutritional Rickets and Osteomalacia in the Twenty-first Century: Revised Concepts, Public Health, and Prevention Strategies.

PubMed

Uday, Suma; Högler, Wolfgang

2017-08-01

Nutritional rickets and osteomalacia are common in dark-skinned and migrant populations. Their global incidence is rising due to changing population demographics, failing prevention policies and missing implementation strategies. The calcium deprivation spectrum has hypocalcaemic (seizures, tetany and dilated cardiomyopathy) and late hypophosphataemic (rickets, osteomalacia and muscle weakness) complications. This article reviews sustainable prevention strategies and identifies areas for future research. The global rickets consensus recognises the equal contribution of vitamin D and dietary calcium in the causation of calcium deprivation and provides a three stage categorisation for sufficiency, insufficiency and deficiency. For rickets prevention, 400 IU daily is recommended for all infants from birth and 600 IU in pregnancy, alongside monitoring in antenatal and child health surveillance programmes. High-risk populations require lifelong supplementation and food fortification with vitamin D or calcium. Future research should identify the true prevalence of rickets and osteomalacia, their role in bone fragility and infant mortality, and best screening and public health prevention tools.

[Tetanus prophylaxis after an injury; check the need for vaccination and immunoglobulin].

PubMed

te Wierik, Margreet J M; Hahné, Susan J M; van Ooik, Paula C; van Lier, Ans M C; Swaan, Corien M

2013-01-01

Tetanus can occur after an injury and is caused by the exotoxin of Clostridium tetani. Characteristics of generalised tetanus include spasms in the back and other muscles, trismus, risus sardonicus and difficulty in breathing caused by laryngospasms. Vaccination through the National Vaccination Programme of the Netherlands has resulted in 94% of the population being protected against tetanus; certain groups, however, have a low rate of vaccination. In the Netherlands, 5 patients were reported to have generalised tetanus in 2011. This figure is relatively high in comparison with previous years. Of these 5 patients, 3 did not receive post-exposure-prophylaxis (PEP) after their injuries, or received it incompletely. PEP may be comprised of 1 or more vaccinations with the tetanus toxoid and/or the administration of tetanus immunoglobulin. Patients who have sustained an injury should be evaluated in accordance with the guideline 'Tetanus' by the Landelijke Coördinatie Infectieziekten (National Coordination Centre for communicable disease control), and to assess whether PEP is indicated.

Diagnosis and management of tetanus outside the intensive care unit: a case report

NASA Astrophysics Data System (ADS)

Bravo, T. E.; Siregar, M. L.; Jamil, K. F.

2018-03-01

Tetanus is an acute, toxin-mediated disease caused by Clostridium tetani infection. Under favorable anaerobic conditions, such as in the unclean environment, necrotic wounds, this ubiquitous bacillus may produce tetanospasmin, an extremely potent neurotoxin. A 38-year-old man was admitted to an emergency room, at Zainoel Abidin General Hospital, with the main complaint of back-muscle stiffness. Based on physical examination, he was fully alert with a slightly rapid breathing, trismus with the maximum oral cavity opening was only about one finger width, but rhisus sardonicus was not evident. Ten days before admission, while gardening, his left foot accidentally stabbed by wooden tree stake. We immediately started a single dose of tetanus immunoglobulin followed by intravenous metronidazole, penicillin G, and intravenous diazepam. Tetanus diagnosed by physical clinical finding. The management of tetanus patients including the use of immunoglobulin and antibiotic therapy, analgesia, sedation and neuromuscular blockade management and mechanical ventilation, the care was delivered outside the Intensive care unit.

[Risk of arrhythmia and domestic low-voltage electrical injury].

PubMed

Claudet, I; Maréchal, C; Debuisson, C; Salanne, S

2010-04-01

Analysis of domestic low-voltage (220-240 V) electrical injury in children admitted to a pediatric emergency department to illustrate the low risk of initial or delayed risk of arrhythmia. Retrospective study between 2001 and 2008 analyzing all children aged less than 15 years admitted for a low-voltage electrical injury. The data collected were age, sex, time and circumstances of the accident, time and day of admission, transport modalities, presence of risk factors for arrhythmia (transthoracic current, wet skin, tetany, loss of consciousness or neurological symptoms, and initial EKG abnormalities), injuries, EKG, muscular and/or cardiac enzyme values, progression and complications. For statistical analysis, data were entered in Microsoft Excel tables. Analysis was done with StatView5.1 (SAS Institute) and Epi Info 6.04fr (VF, ENSP epiconcept). In the descriptive analysis, the data are presented as mean values with SD, median and range. Forty-eight children were included. The mean annual number of admissions was equal to 6 (range, 3-12). The mean age was 6.2 + or - 4.3 years (median, 4.6 years). There was a male predominance: the overall sex ratio was 1.5, i.e., 3 before the age of 2 and 2.6 before the age of 10. The electrical injury occurred after contact with a wire or a connected cord or after the introduction of a metallic object in a wall socket. Ten children had risk factors of arrhythmia (mainly wet skin or thoracic pain). Twenty-nine children suffered from burns to the extremities (digits and hands, 70 %). At admission, 45 children had an EKG performed. The initial EKG was considered abnormal in 8 cases showing: sinusal tachycardia (n=4), incomplete right bundle branch block (n=4), and V(1) negative T waves (n=1). The EKG normalized within the first 12h. Hospitalization for cardiac monitoring was required for 18 children. No delayed arrhythmia occurred. In a mean time of 3.5h after the accident, a troponin dosage was given to 15 children and was normal in all cases. One child developed rhabdomyolysis and evolved without needing dialysis. After a low-voltage electrical injury, initial arrhythmia is not frequent, with often a nonspecific and transitory EKG expression; delayed arrhythmia is very rare. Children presenting to the emergency department after such an electrical accident, who are asymptomatic, without any risk factors for arrhythmia (wet skin, tetany, vertical pathway of the current, preexistent cardiological conditions, loss of consciousness) and with a normal initial EKG do not require cardiac monitoring. Copyright 2010 Elsevier Masson SAS. All rights reserved.

Resurrection of vitamin D deficiency and rickets

PubMed Central

Holick, Michael F.

2006-01-01

The epidemic scourge of rickets in the 19th century was caused by vitamin D deficiency due to inadequate sun exposure and resulted in growth retardation, muscle weakness, skeletal deformities, hypocalcemia, tetany, and seizures. The encouragement of sensible sun exposure and the fortification of milk with vitamin D resulted in almost complete eradication of the disease. Vitamin D (where D represents D2 or D3) is biologically inert and metabolized in the liver to 25-hydroxyvitamin D [25(OH)D], the major circulating form of vitamin D that is used to determine vitamin D status. 25(OH)D is activated in the kidneys to 1,25-dihydroxyvitamin D [1,25(OH)2D], which regulates calcium, phosphorus, and bone metabolism. Vitamin D deficiency has again become an epidemic in children, and rickets has become a global health issue. In addition to vitamin D deficiency, calcium deficiency and acquired and inherited disorders of vitamin D, calcium, and phosphorus metabolism cause rickets. This review summarizes the role of vitamin D in the prevention of rickets and its importance in the overall health and welfare of infants and children. PMID:16886050

Hyperparathyroidism during Pregnancy- A Diagnostic and Therapeutic Challenge

PubMed Central

Sharma, Richa; Bhanupriya; Guleria, Kiran; Suneja, Amita

2017-01-01

Primary Hyperparathyroidism (PHP) is a rare event in pregnancy; Maternal complications in PHP patients can be as high as 67%. It can be overlooked easily because of many similar complaints shared by hyperparathyroidism and pregnancy such as nausea and vomiting, gastritis, bone aches, easy fatigability. Hypercalcemic crisis can develop resulting in coma and death. Neonatal effects are tetany and death in about 80% of cases. We report a case, of an antenatal woman at 30 weeks gestation with complains of painful swelling in left lower jaw and below right knee, pain over right hip joint and frequent episodes of gastritis. She was finally diagnosed to have primary hyperparathyroidism and brown tumour due to parathyroid adenoma. The baby was kept in Neonatal Intensive Care Unit (NICU) for three weeks, in view of prematurity with respiratory distress and later developed sepsis with DIC. The patient’s signs and symptoms regressed after parathyroid surgery and the baby was healthy at the time of discharge. This case highlights the progressive deterioration of the patient because of lack of awareness of this disease process and its impact on maternal and foetal morbidity. PMID:29207788

A case of osteomalacia due to deranged mineral balance caused by saccharated ferric oxide and short-bowel syndrome: A case report.

PubMed

Nomoto, Hiroshi; Miyoshi, Hideaki; Nakamura, Akinobu; Nagai, So; Kitao, Naoyuki; Shimizu, Chikara; Atsumi, Tatsuya

2017-09-01

Saccharated ferric oxide has been shown to lead to elevation of fibroblast growth factor 23, hypophosphatemia, and, consequently, osteomalacia. Moreover, mineral imbalance is often observed in patients with short-bowel syndrome to some degree. A 62-year-old woman with short-bowel syndrome related with multiple resections of small intestines due to Crohn disease received regular intravenous administration of saccharated ferric oxide. Over the course of treatment, she was diagnosed with tetany, which was attributed to hypocalcemia. Additional assessments of the patient revealed not only hypocalcemia, but also hypophosphatemia, hypomagnesemia, osteomalacia, and a high concentration of fibroblast growth factor 23 (314 pg/mL). We diagnosed her with mineral imbalance-induced osteomalacia due to saccharated ferric oxide and short-bowel syndrome. Magnesium replacement therapy and discontinuation of saccharated ferric oxide alone. These treatments were able to normalize her serum mineral levels and increase her bone mineral density. This case suggests that adequate evaluation of serum minerals, including phosphate and magnesium, during saccharated ferric oxide administration may be necessary, especially in patients with short-bowel syndrome.

[Neurology in the medical papyruses of the pharaohs].

PubMed

García-Albea, E

The civilization of Ancient Egypt included a long period of almost three millenniums, and is the most interesting example of the so-called pretechnical archaic cultures. Papyrus scrolls are the main source of information about medical activities. There are fourteen medical papyrus scrolls, in varying states of conservation, mostly corresponding to the Middle Empire, but containing references to the Ancient Empire (the period of the pyramids). These are practical treaties with little explanation of the underlying pathology (a primitive theory of the 'flow' of humors, involving the flowing of different malignant entities) within a system of magic and religion. The empirical observations referring to diseases or dysfunctions of the nervous system, although few, seem to be worth reviewing. Remedies for migraine ('the disorder affecting half the head') take up a long chapter of the only complete and best preserved Ebers papyrus. Dementia (deterioration with age), convulsions and tetany are briefly mentioned in several papyrus scrolls. With the detailed description of the clinical findings of cranial and vertebral trauma, and the orderly assessment of severity presented in Edwin Smith's papyrus the neurology of pharaonic Egypt attained its greatest importance.

A single-dose cytomegalovirus-based vaccine encoding tetanus toxin fragment C induces sustained levels of protective tetanus toxin antibodies in mice.

PubMed

Tierney, Rob; Nakai, Toru; Parkins, Christopher J; Caposio, Patrizia; Fairweather, Neil F; Sesardic, Dorothea; Jarvis, Michael A

2012-04-26

The current commercially available vaccine used to prevent tetanus disease following infection with the anaerobic bacterium Clostridium tetani is safe and effective. However, tetanus remains a major source of mortality in developing countries. In 2008, neonatal tetanus was estimated to have caused >59,000 deaths, accounting for 1% of worldwide infant mortality, primarily in poorer nations. The cost of multiple vaccine doses administered by injection necessary to achieve protective levels of anti-tetanus toxoid antibodies is the primary reason for low vaccine coverage. Herein, we show that a novel vaccine strategy using a cytomegalovirus (CMV)-based vaccine platform induces protective levels of anti-tetanus antibodies that are durable (lasting >13 months) in mice following only a single dose. This study demonstrates the ability of a 'single-dose' CMV-based vaccine strategy to induce durable protection, and supports the potential for a tetanus vaccine based on CMV to impact the incidence of tetanus in developing countries. Copyright © 2012 Elsevier Ltd. All rights reserved.

Optimization of tetanus toxoid ammonium sulfate precipitation process using response surface methodology.

PubMed

Brgles, Marija; Prebeg, Pero; Kurtović, Tihana; Ranić, Jelena; Marchetti-Deschmann, Martina; Allmaier, Günter; Halassy, Beata

2016-10-02

Tetanus toxoid (TTd) is a highly immunogenic, detoxified form of tetanus toxin, a causative agent of tetanus disease, produced by Clostridium tetani. Since tetanus disease cannot be eradicated but is easily prevented by vaccination, the need for the tetanus vaccine is permanent. The aim of this work was to investigate the possibility of optimizing TTd purification, i.e., ammonium sulfate precipitation process. The influence of the percentage of ammonium sulfate, starting amount of TTd, buffer type, pH, temperature, and starting purity of TTd on the purification process were investigated using optimal design for response surface models. Responses measured for evaluation of the ammonium sulfate precipitation process were TTd amount (Lf/mL) and total protein content. These two parameters were used to calculate purity (Lf/mgPN) and the yield of the process. Results indicate that citrate buffer, lower temperature, and lower starting amount of TTd result in higher purities of precipitates. Gel electrophoresis combined with matrix-assisted laser desorption ionization-mass spectrometric analysis of precipitates revealed that there are no inter-protein cross-links and that all contaminating proteins have pIs similar to TTd, so this is most probably the reason for the limited success of purification by precipitation.

Transgenic tomatoes express an antigenic polypeptide containing epitopes of the diphtheria, pertussis and tetanus exotoxins, encoded by a synthetic gene.

PubMed

Soria-Guerra, Ruth Elena; Rosales-Mendoza, Sergio; Márquez-Mercado, Crisóforo; López-Revilla, Rubén; Castillo-Collazo, Rosalba; Alpuche-Solís, Angel Gabriel

2007-07-01

A current priority of vaccinology is the development of multicomponent vaccines that protect against several pathogens. The diphtheria-pertussis-tetanus (DPT) vaccine prevents the symptoms of three serious and often fatal diseases due to the exotoxins produced by Corynebacterium diphteriae, Bordetella pertussis and Clostridium tetani. We are attempting to develop an edible DPT multicomponent vaccine in plants, based on the fusion of protective exotoxin epitopes encoded by synthetic genes. By means of Agrobacterium mediated transformation we generated transgenic tomatoes with a plant-optimised synthetic gene encoding a novel polypeptide containing two adjuvant and six DPT immunoprotective exotoxin epitopes joined by peptide linkers. In transformed tomato plants, integration of the synthetic DPT (sDPT) gene detected by PCR was confirmed by Southern blot, and specific transcripts of the expected molecular size were detected by RT-PCR. Expression of the putative polypeptide encoded by the sDPT gene was detected by immunoassay with specific antibodies to the diphtheria, pertussis and tetanus exotoxins. The sDPT gene is therefore integrated, transcribed and translated as the expected recombinant sDPT multiepitope polypeptide in transgenic tomatoes that constitute a potential edible vaccine.

Effect of proton pump inhibitors on magnesium balance: is there a link to cardiovascular risk?

PubMed

Pisani, Laura Francesca; Filippi, Elisabetta; Vavassori, Sara; Munizio, Nadia; Vecchi, Maurizio; Pastorelli, Luca

2016-03-01

Magnesium (Mg(2+)) is the second most copious element inside human cells and the fourth most abundant positively charged ion in the human body. It is of central importance for a broad variety of physiological processes, including intracellular signaling, neuronal excitability, muscle contraction, bone formation and enzyme activation. Its overall balance is tightly regulated by the concerted actions of the intestine, bones and kidneys. Disturbance of this balance can have serious consequences. Symptoms of hypomagnesaemia include tetany, seizures and cardiac arrhythmias, whereas hypermagnesaemia may cause cardiovascular and neuromuscular abnormalities. Drugs can interfere with Mg(2+) homoeostasis in several ways, and proton-pump inhibitors (PPIs) have been associated with hypomagnesaemia. A better understanding of the molecular mechanisms underlying the adverse effects of these medications on Mg(2+) balance will isuggest ideas for prevention and treatment, and might provide greater insight into Mg(2+) homoeostasis. This review gives an overview of the influence of PPIs on Mg(2+) homoeostasis and provides some understanding of the underlying physiological mechanisms. Moreover, we will discuss the potential link between PPI-induced changes in Mg(2+) homeostasis, and the reported cardiovascular risk observed in long-term PPI users.

A case of osteomalacia due to deranged mineral balance caused by saccharated ferric oxide and short-bowel syndrome

PubMed Central

Nomoto, Hiroshi; Miyoshi, Hideaki; Nakamura, Akinobu; Nagai, So; Kitao, Naoyuki; Shimizu, Chikara; Atsumi, Tatsuya

2017-01-01

Abstract Rationale: Saccharated ferric oxide has been shown to lead to elevation of fibroblast growth factor 23, hypophosphatemia, and, consequently, osteomalacia. Moreover, mineral imbalance is often observed in patients with short-bowel syndrome to some degree. Patient concerns: A 62-year-old woman with short-bowel syndrome related with multiple resections of small intestines due to Crohn disease received regular intravenous administration of saccharated ferric oxide. Over the course of treatment, she was diagnosed with tetany, which was attributed to hypocalcemia. Additional assessments of the patient revealed not only hypocalcemia, but also hypophosphatemia, hypomagnesemia, osteomalacia, and a high concentration of fibroblast growth factor 23 (314 pg/mL). Diagnoses: We diagnosed her with mineral imbalance-induced osteomalacia due to saccharated ferric oxide and short-bowel syndrome. Interventions: Magnesium replacement therapy and discontinuation of saccharated ferric oxide alone. Outcomes: These treatments were able to normalize her serum mineral levels and increase her bone mineral density. Lessons: This case suggests that adequate evaluation of serum minerals, including phosphate and magnesium, during saccharated ferric oxide administration may be necessary, especially in patients with short-bowel syndrome. PMID:28953654

Squeezing at Entrance of Proton Transport Pathway in Proton-translocating Pyrophosphatase upon Substrate Binding*

PubMed Central

Huang, Yun-Tzu; Liu, Tseng-Huang; Lin, Shih-Ming; Chen, Yen-Wei; Pan, Yih-Jiuan; Lee, Ching-Hung; Sun, Yuh-Ju; Tseng, Fan-Gang; Pan, Rong-Long

2013-01-01

Homodimeric proton-translocating pyrophosphatase (H+-PPase; EC 3.6.1.1) is indispensable for many organisms in maintaining organellar pH homeostasis. This unique proton pump couples the hydrolysis of PPi to proton translocation across the membrane. H+-PPase consists of 14–16 relatively hydrophobic transmembrane domains presumably for proton translocation and hydrophilic loops primarily embedding a catalytic site. Several highly conserved polar residues located at or near the entrance of the transport pathway in H+-PPase are essential for proton pumping activity. In this investigation single molecule FRET was employed to dissect the action at the pathway entrance in homodimeric Clostridium tetani H+-PPase upon ligand binding. The presence of the substrate analog, imidodiphosphate mediated two sites at the pathway entrance moving toward each other. Moreover, single molecule FRET analyses after the mutation at the first proton-carrying residue (Arg-169) demonstrated that conformational changes at the entrance are conceivably essential for the initial step of H+-PPase proton translocation. A working model is accordingly proposed to illustrate the squeeze at the entrance of the transport pathway in H+-PPase upon substrate binding. PMID:23720778

Neurologic manifestations of major electrolyte abnormalities.

PubMed

Diringer, M

2017-01-01

The brain operates in an extraordinarily intricate environment which demands precise regulation of electrolytes. Tight control over their concentrations and gradients across cellular compartments is essential and when these relationships are disturbed neurologic manifestations may develop. Perturbations of sodium are the electrolyte disturbances that most often lead to neurologic manifestations. Alterations in extracellular fluid sodium concentrations produce water shifts that lead to brain swelling or shrinkage. If marked or rapid they can result in profound changes in brain function which are proportional to the degree of cerebral edema or contraction. Adaptive mechanisms quickly respond to changes in cell size by either increasing or decreasing intracellular osmoles in order to restore size to normal. Unless cerebral edema has been severe or prolonged, correction of sodium disturbances usually restores function to normal. If the rate of correction is too rapid or overcorrection occurs, however, new neurologic manifestations may appear as a result of osmotic demyelination syndrome. Disturbances of magnesium, phosphate and calcium all may contribute to alterations in sensorium. Hypomagnesemia and hypocalcemia can lead to weakness, muscle spasms, and tetany; the weakness from hypophosphatemia and hypomagnesemia can impair respiratory function. Seizures can be seen in cases with very low concentrations of sodium, magnesium, calcium, and phosphate. © 2017 Elsevier B.V. All rights reserved.

Equine Vaccines: How, When and Why? Report of the Vaccinology Session, French Equine Veterinarians Association, 2016, Reims.

PubMed

Paillot, Romain; Marcillaud Pitel, Christel; D'Ablon, Xavier; Pronost, Stéphane

2017-12-04

To date, vaccination is one of the most efficient methods of prevention against equine infectious diseases. The vaccinology session, which was organised during the annual meeting of the French Equine Veterinarians Association (AVEF) at Reims (France) in 2016, aimed to approach three subjects of importance for the equine industry. Vaccination against three major equine diseases were used as examples: equine influenza (equine influenza virus), rhinopneumonitis (equine herpes virus 1/4), and tetanus ( Clostridium tetani neuro-toxin). (1) Emergency vaccination: while it has been very successful to reduce the impact of equine influenza epizooties and it is also recommended for tetanus in case of surgery and accident, the benefit of emergency vaccination against equine herpes virus 1/4 remains arguable; (2) Compatibility of equine vaccines from different brands: despite being a frequent concerns for equine veterinarians, little information is available about the compatibility of equine vaccines from different commercial origins. The consequence of mixing different equine vaccines targeting the same disease is believed to be limited but scientific evidences are sparse; and, (3) Laps vaccination and vaccine shortage: they could have serious consequences in terms of protection and their impact should be evaluated on a case by case basis, taking into account the risk of contact with the pathogen and the effect on herd immunity.

A case of tetanus infection in an adult with a protective tetanus antibody level.

PubMed

Vollman, Kristan E; Acquisto, Nicole M; Bodkin, Ryan P

2014-04-01

Tetanus is a bacterial infection caused by Clostridium tetani and most commonly presents as trismus or other muscle spasms. Despite the development of the tetanus toxoid vaccine, tetanus infection has not been eradicated. Additionally, while there are hypothesized protective levels of tetanus antibody, tetanus infection may still occur in properly vaccinated individuals. We report the case of a 31-year-old male that presented to the emergency department (ED) with a 2-day history of neck and jaw pain. He reports puncturing his hand with a rusty nail 10 days prior. His reported vaccination history was that he received his last booster vaccination 13 years prior to presentation. In the ED, tetanus vaccine, tetanus immune globulin, and metronidazole were administered. His symptoms improved over the next 2 days and resolved at day 6. Despite his presentation of tetanus infection and rule out of other causes for his symptoms, his tetanus antibody level was reported at 8.4 U/mL, which is considered to be protective.A tetanus antibody level that is adequate for protective immunity should not preclude a patient from treatment of tetanus infection. This case demonstrates that a thorough history, physical exam, and rule out of other causes should guide treatment when there is concern for a tetanus infection.

Classification of involuntary movements in dogs: Tremors and twitches.

PubMed

Lowrie, Mark; Garosi, Laurent

2016-08-01

This review focuses on important new findings in the field of involuntary movements (IM) in dogs and illustrates the importance of developing a clear classification tool for diagnosing tremor and twitches. Developments over the last decade have changed our understanding of IM and highlight several caveats in the current tremor classification. Given the ambiguous association between tremor phenomenology and tremor aetiology, a more cautious definition of tremors based on clinical assessment is required. An algorithm for the characterisation of tremors is presented herein. The classification of tremors is based on the distinction between tremors that occur at rest and tremors that are action-related; tremors associated with action are divided into postural or kinetic. Controversial issues are outlined and thus reflect the open questions that are yet to be answered from an evidence base of peer-reviewed published literature. Peripheral nerve hyper-excitability (PNH; cramps and twitches) may manifest as fasciculations, myokymia, neuromyotonia, cramps, tetany and tetanus. It is anticipated that as we learn more about the aetiology and pathogenesis of IMs, future revisions to the classification will be needed. It is therefore the intent of this work to stimulate discussions and thus contribute to the development of IM research. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Respiratory failure in tetanic patient: maintenance of airway problem in intensive care unit setting

NASA Astrophysics Data System (ADS)

Utami, I. N.; Arifin; Susilo, R. S. B.; Redhono, D.; Sumandjar, T.

2018-03-01

Tetanus is a toxin-mediated disease caused by Clostridium tetani resulting in muscular stiffness and painful spasm. The case fatality rates are high (10-80%), and the most frequent cause of mortality is airway problem that results in respiratory failure. A 52-year-old malecame to the hospital with lockjaw, rhesussardonicus, opisthotonus, and seizure for the last 12 hours, diagnosed with tetanus grade II. We placed the patient in an isolation room, gave 3000U tetanus immunoglobulin, 20mg diazepam in 500ml dextrose 5%/8 hours, and 500mg/6hrs metronidazole. On the seventh day, seizure became frequent, respiratory rate increased with crackles found on the auscultation, and the blood gas analysis showed respiratory failure type II (PCO2 53mmHg). The patientwas immediately sent to the ICU, intubated and given ventilator support. The patientwas sedated with continuous injection of midazolam 3 mg/h, morphine 10mcg/kgBW/h and also levofloxacin 750mg/24hours. Bronchoalveolar lavage culture was positive for Acinetobacter baumanii, so we changed the antibiotic to amikacin injection 500 mg/8hrs. After four days, we extubated the ventilator and transferred from HCU three days later. The patient was fully recovered and discharged after eighteen days of hospitalization.

CRYSTAL STRUCTURE OF CLOSTRIDIUM BOTULINUM NEUROTOXIN SEROTYPE B.

DOE Office of Scientific and Technical Information (OSTI.GOV)

SWAMINATHAN,S.; ESWARAMOORTHY,S.

2001-11-19

The toxigenic strains of Clostridium botulinum produce seven serologically distinct types of neurotoxins labeled A - G (EC 3.4.24.69), while Clostridium tetani produces tetanus neurotoxin (EC 3.4.24.68). Botulinum and tetanus neurotoxins (BoNTs and TeNT) are produced as single inactive chains of molecular mass of approximately 150 kDa. Most of these neurotoxins are released after being cleaved into two chains, a heavy chain (HI) of 100 kDa and a light chain (L) of 50 kDa held together by an interchain disulfide bond, by tissue proteinases. BoNT/E is released as a single chain but cleaved by host proteinases [1]. Clostvidium botulinum neurotoxinsmore » are extremely poisonous proteins with their LD{sub 50} for humans in the range of 0.1 - 1 ng kg{sup -1} [2]. Botulinum neurotoxins are responsible for neuroparalytic syndromes of botulism characterized by serious neurological disorders and flaccid paralysis. BoNTs block the release of acetylcholine at the neuromuscular junction causing flaccid paralysis while TeNT blocks the release of neurotransmitters like glycine and {gamma}-aminobutyric acid (GABA) in the inhibitory interneurons of the spinal cord resulting in spastic paralysis. In spite of different clinical symptoms, their aetiological agents intoxicate neuronal cells in the same way and these toxins have similar structural organization [3].« less

Myokymia and neuromyotonia in veterinary medicine: a comparison with peripheral nerve hyperexcitability syndrome in humans.

PubMed

Vanhaesebrouck, An E; Bhatti, Sofie F M; Franklin, Robin J M; Van Ham, Luc

2013-08-01

Involuntary muscle hyperactivity can result from muscle or peripheral nerve hyperexcitability or central nervous system dysfunction. In humans, diseases causing hyperexcitability of peripheral nerves are grouped together under the term 'peripheral nerve hyperexcitability' (PNH). Hyperexcitability of the peripheral motor nerve can result into five different phenotypic main variants, i.e. fasciculations, myokymia, neuromyotonia, cramps and tetany, each with their own clinical and electromyographic characteristics. This review focuses on the most commonly described expressions of PNH in veterinary medicine, i.e. myokymia and neuromyotonia, in particular in young Jack Russell terriers. Data from 58 veterinary cases with generalized myokymia and neuromyotonia were analyzed, including unpublished treatment and follow-up data on eight Jack Russell terriers from a previous study and seven additional Jack Russell terriers. A dysfunction of the potassium channel or its associated proteins has been found in many human syndromes characterized by PNH, in particular in generalized myokymia and neuromyotonia, and is suspected to occur in veterinary medicine. Potential pathomechanisms of potassium channel dysfunction leading to signs of PNH are broad and include genetic mutations, antibody-mediated attack or ion channel maldistribution due to axonal degeneration or demyelination. A more accurate classification of the different PNH syndromes will facilitate a more rapid diagnosis and guide further research into natural occurring PNH in animals. Copyright © 2013 Elsevier Ltd. All rights reserved.

Rickets: case series and diagnostic review of hypovitaminosis D in swine.

PubMed

Madson, Darin M; Ensley, Steve M; Gauger, Phil C; Schwartz, Kent J; Stevenson, Greg W; Cooper, Vickie L; Janke, Bruce H; Burrough, Eric R; Goff, Jesse P; Horst, Ronald L

2012-11-01

Rickets can be attributed to nutritional, genetic, hormonal, or toxic disturbances and is classified as a metabolic bone disease. Rickets is most often associated with inappropriate dietary levels of calcium, phosphorus, and/or vitamin D. During a 27-month period (January 2010 through March 2012), the Iowa State University Veterinary Diagnostic Laboratory investigated causes of sudden, unexpected death and lameness in growing pigs throughout the Midwestern United States. Clinical observations from 17 growing pig cases included weakness, lameness, reluctance to move, muscle fasciculations and/or tremors, tetany, and death. Ribs were weak, soft, and bent prior to breaking; rachitic lesions were apparent at costochondral junctions in multiple cases. Acute and/or chronic bone fractures were also noted in multiple bones. Failure of endochondral ossification, expanded physes, infractions, thin trabeculae, and increased osteoclasts were noted microscopically. Decreased bone ash and serum 25(OH)D(3), combined with clinical and microscopic evaluation, confirmed a diagnosis of vitamin D-dependent rickets in all cases. In 3 cases, disease was linked to a specific nutrient supplier that ultimately resulted in a voluntary feed recall; however, most cases in the current investigation were not associated with a particular feed company. The present report describes vitamin D-associated rickets and its importance as a potential cause of weakness, lameness, muscle fasciculations, recumbency or sudden unexpected death in swine, and describes appropriate samples and tests for disease diagnosis.

Equine Vaccines: How, When and Why? Report of the Vaccinology Session, French Equine Veterinarians Association, 2016, Reims

PubMed Central

Paillot, Romain; Marcillaud Pitel, Christel; D’Ablon, Xavier; Pronost, Stéphane

2017-01-01

To date, vaccination is one of the most efficient methods of prevention against equine infectious diseases. The vaccinology session, which was organised during the annual meeting of the French Equine Veterinarians Association (AVEF) at Reims (France) in 2016, aimed to approach three subjects of importance for the equine industry. Vaccination against three major equine diseases were used as examples: equine influenza (equine influenza virus), rhinopneumonitis (equine herpes virus 1/4), and tetanus (Clostridium tetani neuro-toxin). (1) Emergency vaccination: while it has been very successful to reduce the impact of equine influenza epizooties and it is also recommended for tetanus in case of surgery and accident, the benefit of emergency vaccination against equine herpes virus 1/4 remains arguable; (2) Compatibility of equine vaccines from different brands: despite being a frequent concerns for equine veterinarians, little information is available about the compatibility of equine vaccines from different commercial origins. The consequence of mixing different equine vaccines targeting the same disease is believed to be limited but scientific evidences are sparse; and, (3) Laps vaccination and vaccine shortage: they could have serious consequences in terms of protection and their impact should be evaluated on a case by case basis, taking into account the risk of contact with the pathogen and the effect on herd immunity. PMID:29207516

Electrofishing power requirements in relation to duty cycle

USGS Publications Warehouse

Miranda, L.E.; Dolan, C.R.

2004-01-01

Under controlled laboratory conditions we measured the electrical peak power required to immobilize (i.e., narcotize or tetanize) fish of various species and sizes with duty cycles (i.e., percentage of time a field is energized) ranging from 1.5% to 100%. Electrofishing effectiveness was closely associated with duty cycle. Duty cycles of 10-50% required the least peak power to immobilize fish; peak power requirements increased gradually above 50% duty cycle and sharply below 10%. Small duty cycles can increase field strength by making possible higher instantaneous peak voltages that allow the threshold power needed to immobilize fish to radiate farther away from the electrodes. Therefore, operating within the 10-50% range of duty cycles would allow a larger radius of immobilization action than operating with higher duty cycles. This 10-50% range of duty cycles also coincided with some of the highest margins of difference between the electrical power required to narcotize and that required to tetanize fish. This observation is worthy of note because proper use of duty cycle could help reduce the mortality associated with tetany documented by some authors. Although electrofishing with intermediate duty cycles can potentially increase effectiveness of electrofishing, our results suggest that immobilization response is not fully accounted for by duty cycle because of a potential interaction between pulse frequency and duration that requires further investigation.

Isolation of acetic, propionic and butyric acid-forming bacteria from biogas plants.

PubMed

Cibis, Katharina Gabriela; Gneipel, Armin; König, Helmut

2016-02-20

In this study, acetic, propionic and butyric acid-forming bacteria were isolated from thermophilic and mesophilic biogas plants (BGP) located in Germany. The fermenters were fed with maize silage and cattle or swine manure. Furthermore, pressurized laboratory fermenters digesting maize silage were sampled. Enrichment cultures for the isolation of acid-forming bacteria were grown in minimal medium supplemented with one of the following carbon sources: Na(+)-dl-lactate, succinate, ethanol, glycerol, glucose or a mixture of amino acids. These substrates could be converted by the isolates to acetic, propionic or butyric acid. In total, 49 isolates were obtained, which belonged to the phyla Firmicutes, Tenericutes or Thermotogae. According to 16S rRNA gene sequences, most isolates were related to Clostridium sporosphaeroides, Defluviitoga tunisiensis and Dendrosporobacter quercicolus. Acetic, propionic or butyric acid were produced in cultures of isolates affiliated to Bacillus thermoamylovorans, Clostridium aminovalericum, Clostridium cochlearium/Clostridium tetani, C. sporosphaeroides, D. quercicolus, Proteiniborus ethanoligenes, Selenomonas bovis and Tepidanaerobacter sp. Isolates related to Thermoanaerobacterium thermosaccharolyticum produced acetic, butyric and lactic acid, and isolates related to D. tunisiensis formed acetic acid. Specific primer sets targeting 16S rRNA gene sequences were designed and used for real-time quantitative PCR (qPCR). The isolates were physiologically characterized and their role in BGP discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Quasi-elastic light-scattering studies of single skeletal muscle fibers.

PubMed Central

Haskell, R C; Carlson, F D

1981-01-01

Measurements were made of the intensity autocorrelation function, g(2)[tau], of light scattered from intact frog muscle fibers. During the tension plateau of an isometric tenanus, scattered field statistics were approximately Gaussian and intensity fluctuations were quasi-stationary. The half time, tau 1/2, for the decay of g(2)[tau] was typically 70 ms at a scattering angle of 30 degrees. The decay rate, 1/tau 1/2, of g(2)[tau] varied roughly linearly with the projection of the scattering vector on the fiber axis. 1/tau 1/2 was greater during the tension creep phase of tetani of highly stretched fibers, but was roughly independent of sarcomere length during the tension plateau. g(2)[tau] measured during rest or on diffraction pattern maxima during isometric contraction were flat with low amplitudes. These results are consistent with a model of a 200-mu m segment of an isometrically contracting fiber in which scattering material possesses relative axial velocities of 1-2 mu m/s accompanied by relative axial displacements greater than 0.1 mu m. The slow (1-2 mu m/s) motion of one portion of the fiber relative to another observed under the microscope (500X) during isometric contraction is consistent with the light-scattering results. Structural fluctuations on the scale of the myofibrillar sarcomere which may arise from asynchronous cycling of cross-bridges must involve relative axial velocities less than 3 mu m/s or relative axial displacements less than 0.05 mu m. PMID:6974014

Bacterial community structure transformed after thermophilically composting human waste in Haiti

PubMed Central

Kramer, Sasha; Roy, Monika; Reid, Francine C.; Dubinsky, Eric A.

2017-01-01

Recycling human waste for beneficial use has been practiced for millennia. Aerobic (thermophilic) composting of sewage sludge has been shown to reduce populations of opportunistically pathogenic bacteria and to inactivate both Ascaris eggs and culturable Escherichia coli in raw waste, but there is still a question about the fate of most fecal bacteria when raw material is composted directly. This study undertook a comprehensive microbial community analysis of composting material at various stages collected over 6 months at two composting facilities in Haiti. The fecal microbiota signal was monitored using a high-density DNA microarray (PhyloChip). Thermophilic composting altered the bacterial community structure of the starting material. Typical fecal bacteria classified in the following groups were present in at least half the starting material samples, yet were reduced below detection in finished compost: Prevotella and Erysipelotrichaceae (100% reduction of initial presence), Ruminococcaceae (98–99%), Lachnospiraceae (83–94%, primarily unclassified taxa remained), Escherichia and Shigella (100%). Opportunistic pathogens were reduced below the level of detection in the final product with the exception of Clostridium tetani, which could have survived in a spore state or been reintroduced late in the outdoor maturation process. Conversely, thermotolerant or thermophilic Actinomycetes and Firmicutes (e.g., Thermobifida, Bacillus, Geobacillus) typically found in compost increased substantially during the thermophilic stage. This community DNA-based assessment of the fate of human fecal microbiota during thermophilic composting will help optimize this process as a sanitation solution in areas where infrastructure and resources are limited. PMID:28570610

Effects of hypothyroidism on the skeletal muscle blood flow response to contractions.

PubMed

Bausch, L; McAllister, R M

2003-04-01

Hypothyroidism is associated with impaired blood flow to skeletal muscle under whole body exercise conditions. It is unclear whether poor cardiac and/or vascular function account for blunted muscle blood flow. Our experiment isolated a small group of hindlimb muscles and simulated exercise via tetanic contractions. We hypothesized that muscle blood flow would be attenuated in hypothyroid rats (HYPO) compared with euthyroid rats (EUT). Rats were made hypothyroid by mixing propylthiouracil in their drinking water (2.35 x 10-3 mol/l). Treatment efficacy was evidenced by lower serum T3 concentrations and resting heart rates in HYPO (both P<0.05). In the experimental preparation, isometric contractions of the lower right hindlimb muscles at a rate of 30 tetani/min were induced via sciatic nerve stimulation. Regional blood flows were determined by the radiolabelled microsphere method at three time points: rest, 2 min of contractions and 10 min of contractions. Muscle blood flow generally increased from rest ( approximately 5-10 ml/min per 100 g) through contractions for both groups. Further, blood flow during contractions did not differ between groups for any muscle (eg. red section of gastrocnemius muscle; EUT, 59.9 +/- 14.1; HYPO, 61.1 +/- 15.0; NS between groups). These findings indicate that hypothyroidism does not significantly impair skeletal muscle blood flow when only a small muscle mass is contracting. Our findings suggest that impaired blood flow under whole body exercise is accounted for by inadequate cardiac function rather than abnormal vascular function.

Oral immunogenicity of tomato-derived sDPT polypeptide containing Corynebacterium diphtheriae, Bordetella pertussis and Clostridium tetani exotoxin epitopes.

PubMed

Soria-Guerra, Ruth E; Rosales-Mendoza, Sergio; Moreno-Fierros, Leticia; López-Revilla, Rubén; Alpuche-Solís, Angel G

2011-03-01

DPT vaccine, designed to immunize against diphtheria, pertussis, and tetanus, has been shown to be effective in humans. Nevertheless, dissatisfaction with the whole-cell preparations is due to the reactogenicity, which has to lead to the development of new safer formulations. Previously, we described the expression in tomato of a plant-optimized synthetic gene encoding the recombinant polypeptide sDPT, containing mainly immunoprotective epitopes of the diphtheria, pertussis and tetanus exotoxins and two adjuvants. In this study, we examined whether the ingestion of tomato-derived sDPT protein induces specific antibodies in mice after three weekly doses scheme. A positive group immunized with DPT toxoids was included. Specific antibody levels were assessed in serum, gut and lung. Sera tested for IgG antibody response to pertussis, tetanus and diphtheria toxin showed responses to the foreign antigens; interestingly, the response to diphtheria epitope was similar to those observed in the positive group. We found higher IgG1 than IgG2a responses in serum. A modest IgG response was observed in the tracheopulmonary fluid. High response of IgA against tetanus toxin was evident in gut, which was statistically comparable to that obtained in the positive group. The levels of response in these groups were higher than those in mice that received wild-type tomato. These findings support the concept of using transgenic tomatoes expressing sDPT polypeptide as model for edible vaccine against diphtheria, pertussis, and tetanus.

Tetanus Neurotoxin Neutralizing Antibodies Screened from a Human Immune scFv Antibody Phage Display Library.

PubMed

Wang, Han; Yu, Rui; Fang, Ting; Yu, Ting; Chi, Xiangyang; Zhang, Xiaopeng; Liu, Shuling; Fu, Ling; Yu, Changming; Chen, Wei

2016-09-11

Tetanus neurotoxin (TeNT) produced by Clostridium tetani is one of the most poisonous protein substances. Neutralizing antibodies against TeNT can effectively prevent and cure toxicosis. Using purified Hc fragments of TeNT (TeNT-Hc) as an antigen, three specific neutralizing antibody clones recognizing different epitopes were selected from a human immune scFv antibody phage display library. The three antibodies (2-7G, 2-2D, and S-4-7H) can effectively inhibit the binding between TeNT-Hc and differentiated PC-12 cells in vitro. Moreover, 2-7G inhibited TeNT-Hc binding to the receptor via carbohydrate-binding sites of the W pocket while 2-2D and S-4-7H inhibited binding of the R pocket. Although no single mAb completely protected mice from the toxin, they could both prolong survival when challenged with 20 LD50s (50% of the lethal dose) of TeNT. When used together, the mAbs completely neutralized 1000 LD50s/mg Ab, indicating their high neutralizing potency in vivo. Antibodies recognizing different carbohydrate-binding pockets could have higher synergistic toxin neutralization activities than those that recognize the same pockets. These results could lead to further production of neutralizing antibody drugs against TeNT and indicate that using TeNT-Hc as an antigen for screening human antibodies for TeNT intoxication therapy from human immune antibody library was convenient and effective.

2D DIGE Does Not Reveal all: A Scotopic Report Suggests Differential Expression of a Single "Calponin Family Member" Protein for Tetany of Sphincters!

PubMed

Chaudhury, Arun

2015-01-01

Using 2D differential gel electrophoresis (DIGE) and mass spectrometry (MS), a recent report by Rattan and Ali (2015) compared proteome expression between tonically contracted sphincteric smooth muscles of the internal anal sphincter (IAS), in comparison to the adjacent rectum [rectal smooth muscles (RSM)] that contracts in a phasic fashion. The study showed the differential expression of a single 23 kDa protein SM22, which was 1.87 fold, overexpressed in RSM in comparison to IAS. Earlier studies have shown differences in expression of different proteins like Rho-associated protein kinase II, myosin light chain kinase, myosin phosphatase, and protein kinase C between IAS and RSM. The currently employed methods, despite its high-throughput potential, failed to identify these well-characterized differences between phasic and tonic muscles. This calls into question the fidelity and validatory potential of the otherwise powerful technology of 2D DIGE/MS. These discrepancies, when redressed in future studies, will evolve this recent report as an important baseline study of "sphincter proteome." Proteomics techniques are currently underutilized in examining pathophysiology of hypertensive/hypotensive disorders involving gastrointestinal sphincters, including achalasia, gastroesophageal reflux disease (GERD), spastic pylorus, seen during diabetes or chronic chemotherapy, intestinal pseudo-obstruction, and recto-anal incontinence. Global proteome mapping may provide instant snapshot of the complete repertoire of differential proteins, thus expediting to identify the molecular pathology of gastrointestinal motility disorders currently labeled "idiopathic" and facilitating practice of precision medicine.

Chelation of hippocampal zinc enhances long-term potentiation and synaptic tagging/capture in CA1 pyramidal neurons of aged rats: implications to aging and memory.

PubMed

Shetty, Mahesh Shivarama; Sharma, Mahima; Sajikumar, Sreedharan

2017-02-01

Aging is associated with decline in cognitive functions, prominently in the memory consolidation and association capabilities. Hippocampus plays a crucial role in the formation and maintenance of long-term associative memories, and a significant body of evidence shows that impairments in hippocampal function correlate with aging-related memory loss. A number of studies have implicated alterations in hippocampal synaptic plasticity, such as long-term potentiation (LTP), in age-related cognitive decline although exact mechanisms underlying are not completely clear. Zinc deficiency and the resultant adverse effects on cognition have been well studied. However, the role of excess of zinc in synaptic plasticity, especially in aging, is not addressed well. Here, we have investigated the hippocampal zinc levels and the impairments in synaptic plasticity, such as LTP and synaptic tagging and capture (STC), in the CA1 region of acute hippocampal slices from 82- to 84-week-old male Wistar rats. We report increased zinc levels in the hippocampus of aged rats and also deficits in the tetani-induced and dopaminergic agonist-induced late-LTP and STC. The observed deficits in synaptic plasticity were restored upon chelation of zinc using a cell-permeable chelator. These data suggest that functional plasticity and associativity can be successfully established in aged neural networks by chelating zinc with cell-permeable chelating agents. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Validity of early parathyroid hormone assay as a diagnostic tool for sub-total thyroidectomy related hypocalcaemia.

PubMed

Riaz, Umbreen; Shah, Syed Aslam; Zahoor, Imran; Riaz, Arsalan; Zubair, Muhammad

2014-07-01

To determine the validity of early (one hour postoperatively) parathyroid hormone (PTH) assay (² 10 pg/ml), keeping gold standard as the serum ionic calcium level, for predicting sub-total thyroidectomy-related hypocalcaemia and to calculate the sensitivity and specificity of latent signs of tetany. Cross-sectional validation study. Department of General Surgery, Pakistan Institute of Medical Sciences, Islamabad from August 2008 to August 2010. Patients undergoing sub-total thyroidectomy were included by convenience sampling. PTH assay was performed 1 hour post sub-total thyroidectomy. Serum calcium levels were performed at 24 and 48 hours, 5th day and 2 weeks after surgery. Cases that developed hypocalcaemia were followed-up for a period of 6 months with monthly calcium level estimation to identify cases of permanent hypocalcaemia. Symptoms and signs of hypocalcaemia manifesting in our patients were recorded. Data was analyzed through SPSS version 10. 2 x 2 tables were used to calculate sensitivity and specificity of PTH in detecting post-thyroidectomy hypocalcaemia. Out of a total of 110 patients included in the study, 16.36% (n=18) developed hypocalcaemia including 1.81% (n=2) cases of permanent hypoparathyroidism. The sensitivity of one hour postoperative PTH assay as a predictive tool for post-thyroidectomy related hypocalcaemia was 94.4% while its specificity was 83.6% with 53% positive predictive value and 98.7% negative predictive value. One hour post sub-total thyroidectomy PTH assay can be helpful in predicting post sub-total thyroidectomy hypocalcaemia. Moreover, it can be useful in safe discharge of day-care thyroidectomy patients.

Congenital rickets due to vitamin D deficiency in the mothers.

PubMed

Paterson, Colin R; Ayoub, David

2015-10-01

We wished to review all published reports of congenital rickets to identify the causes and characteristics. 25 cases were identified in 19 published reports in which there was radiological and/or histological evidence of rickets in the first two weeks after birth. Cases of rickets associated with maternal renal failure were excluded as were infants born at less than 32 weeks gestation. There was evidence of maternal deficiency in 24 of these cases. In 16 cases the diagnosis of the rickets led to the identification of symptomatic osteomalacia in the mothers. Of the 12 mothers who had assays for serum 25-hydroxyvitamin D (25OHD) 11 had values less than 10 ng/mL. Presentations in the infants included craniotabes, wide skull sutures, rachitic rosaries, enlargement of the wrists, tetany and convulsions. In two cases rickets had been suspected from antenatal X-rays. In five cases fractures were found at the time of initial presentation. Of the 16 infants with serum calcium assays 15 had values lower than 8.8 mg/dL. Of 13 infants who had serum alkaline phosphatase assays 12 had abnormally high levels. Of the seven infants in whom serum 25OHD was measured before treatment, all had values less than 10 ng/mL. These reports provide strong support for the view that maternal deficiency leads to overt bone disease from before birth. Maternal deficiency probably also leads to impairment of bone quality in postnatal life. The importance of ensuring adequate vitamin D nutrition in pregnancy is emphasised. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

History and Practice: Antibodies in Infectious Diseases.

PubMed

Hey, Adam

2015-04-01

Antibodies and passive antibody therapy in the treatment of infectious diseases is the story of a treatment concept which dates back more than 120 years, to the 1890s, when the use of serum from immunized animals provided the first effective treatment options against infections with Clostridium tetani and Corynebacterium diphtheriae. However, after the discovery of penicillin by Fleming in 1928, and the subsequent introduction of the much cheaper and safer antibiotics in the 1930s, serum therapy was largely abandoned. However, the broad and general use of antibiotics in human and veterinary medicine has resulted in the development of multi-resistant strains of bacteria with limited to no response to existing treatments and the need for alternative treatment options. The combined specificity and flexibility of antibody-based treatments makes them very valuable tools for designing specific antibody treatments to infectious agents. These attributes have already caused a revolution in new antibody-based treatments in oncology and inflammatory diseases, with many approved products. However, only one monoclonal antibody, palivizumab, for the prevention and treatment of respiratory syncytial virus, is approved for infectious diseases. The high cost of monoclonal antibody therapies, the need for parallel development of diagnostics, and the relatively small markets are major barriers for their development in the presence of cheap antibiotics. It is time to take a new and revised look into the future to find appropriate niches in infectious diseases where new antibody-based treatments or combinations with existing antibiotics, could prove their value and serve as stepping stones for broader acceptance of the potential for and value of these treatments.

Effects of lymphatic drainage and local cryo exposition regeneration after high-intensive exercises

PubMed Central

Behringer, Michael; Jedlicka, Diana; McCourt, Molly; Ring, Matthias; Mester, Joachim

2016-01-01

Summary Background Recovery from exercise and competition is important in sports medicine, particularly when rest periods are short. The objective is to determine the efficacy of cryo exposition (CRY) and manual lymphatic drainage (MLD) to hasten short term recovery of muscle performance after eccentric contractions. Methods In a randomized controlled trial, 30 healthy sport students (21 males, 9 females; age: 25.7±2.8 years) performed 4×20 eccentric contractions of knee extensors, followed by 30 min MLD, CRY, or rest (RST) under controlled laboratory environment. Maximal voluntary contractions (MVC), electrically induced muscle fatigue (FI), and electrically induced tetani (EIT) at low (T2: 20 Hz) and high frequencies were tested. Results Force decline and recovery kinetics regarding MVC, FI, and EIT did not differ significantly (p<0.05) between groups. That is, 24 h after the intervention, MVC (MLD: 80.9±5.5%; CRY: 81.1±8.5%; RST: 83.5±7.3%), FI (MLD: 83.2±23.7%; CRY: 81.2±38.8%; RST: 93.2±22.9%), and EIT (T1: MLD: 53.0±29.5%; CRY: 39.0±32.9%; RST: 46.3±26.1%; T2: MLD: 84.2±27.2%; CRY: 64.2±24.2%; RST: 66.6±22.3%) were similarly depressed irrespective of applied treatments. Conclusion Neither CRY nor MLD hastened the recovery of muscle performance, when applied for 30 min. Identification number of the Primary Registry Network: DRKS00007608. PMID:27900297

Tetanus surveillance --- United States, 2001-2008.

PubMed

2011-04-01

Tetanus is a life-threatening but preventable disease caused by the toxin of Clostridium tetani, a ubiquitous, spore-forming, gram-positive bacillus found in high concentrations in soil and animal excrement. Reported tetanus cases have declined >95%, and deaths from tetanus have declined >99% in the United States since 1947, when the disease became reportable nationally. To update a previous report and to determine the populations at greatest risk for the disease, CDC analyzed cases reported to the National Notifiable Diseases Surveillance System (NNDSS) during 2001--2008. This report summarizes the results of that analysis, which found that 233 tetanus cases were reported during 2001--2008; among the 197 cases with known outcomes, the case-fatality rate was 13.2%. Average annual incidence during that period was 0.10 per 1 million population overall and 0.23 among persons aged ≥65 years. Incidence among Hispanics was nearly twice that among non-Hispanics, a difference accounted for by 16 cases among Hispanic injection drug users (IDUs). Among the 92 patients for whom tetanus toxoid-containing (TT) vaccination status was available, 37 (40.2%) had received no doses of TT vaccine. Thirty (15.4%) of 195 patients had diabetes, and 27 (15.3%) of 176 were IDUs. Of 51 patients with an acute wound and a surveillance report complete enough to evaluate tetanus prophylaxis, 49 (96.1%) had not received appropriate prophylaxis. Tetanus remains a rare but life-threatening disease in the United States. Health-care providers should ensure up-to-date TT vaccination of all their patients, especially persons aged ≥65 years, persons with diabetes, and injection drug users.

Two Pathways of Glutamate Fermentation by Anaerobic Bacteria

PubMed Central

Buckel, Wolfgang; Barker, H. A.

1974-01-01

Two pathways are involved in the fermentation of glutamate to acetate, butyrate, carbon dioxide, and ammonia—the methylaspartate and the hydroxyglutarate pathways which are used by Clostridium tetanomorphum and Peptococcus aerogenes, respectively. Although these pathways give rise to the same products, they are easily distinguished by different labeling patterns of the butyrate when [4-14C]glutamate is used as substrate. Schmidt degradation of the radioactive butyrate from C. tetanomorphum yielded equally labeled propionate and carbon dioxide, whereas nearly all the radioactivity of the butyrate from P. aerogenes was recovered in the corresponding propionate. This procedure was used as a test for the pathway of glutamate fermentation by 15 strains (9 species) of anaerobic bacteria. The labeling patterns of the butyrate indicate that glutamate is fermented via the methylaspartate pathway by C. tetani, C. cochlearium, and C. saccarobutyricum, and via the hydroxyglutarate pathway by Acidaminococcus fermentans, C. microsporum, Fusobacterium nucleatum, and F. fusiformis. Enzymes specific for each pathway were assayed in crude extracts of the above organisms. 3-Methylaspartase was found only in clostridia which use the methylaspartate pathway, including Clostridium SB4 and C. sticklandii, which probably degrade glutamate to acetate and carbon dioxide by using a second amino acid as hydrogen acceptor. High levels of 2-hydroxyglutarate dehydrogenase were found exclusively in organisms that use the hydroxyglutarate pathway. The data indicate that only two pathways are involved in the fermentation of glutamate by the bacteria analyzed. The methylaspartate pathway appears to be used only by species of Clostridium, whereas the hydroxyglutarate pathway is used by representatives of several genera. PMID:4813895

Reactive oxygen species and fatigue-induced prolonged low-frequency force depression in skeletal muscle fibres of rats, mice and SOD2 overexpressing mice.

PubMed

Bruton, Joseph D; Place, Nicolas; Yamada, Takashi; Silva, José P; Andrade, Francisco H; Dahlstedt, Anders J; Zhang, Shi-Jin; Katz, Abram; Larsson, Nils-Göran; Westerblad, Håkan

2008-01-01

Skeletal muscle often shows a delayed force recovery after fatiguing stimulation, especially at low stimulation frequencies. In this study we focus on the role of reactive oxygen species (ROS) in this fatigue-induced prolonged low-frequency force depression. Intact, single muscle fibres were dissected from flexor digitorum brevis (FDB) muscles of rats and wild-type and superoxide dismutase 2 (SOD2) overexpressing mice. Force and myoplasmic free [Ca(2+)] ([Ca(2+)](i)) were measured. Fibres were stimulated at different frequencies before and 30 min after fatigue induced by repeated tetani. The results show a marked force decrease at low stimulation frequencies 30 min after fatiguing stimulation in all fibres. This decrease was associated with reduced tetanic [Ca(2+)](i) in wild-type mouse fibres, whereas rat fibres and mouse SOD2 overexpressing fibres instead displayed a decreased myofibrillar Ca(2+) sensitivity. The SOD activity was approximately 50% lower in wild-type mouse than in rat FDB muscles. Myoplasmic ROS increased during repeated tetanic stimulation in rat fibres but not in wild-type mouse fibres. The decreased Ca(2+) sensitivity in rat fibres could be partially reversed by application of the reducing agent dithiothreitol, whereas the decrease in tetanic [Ca(2+)](i) in wild-type mouse fibres was not affected by dithiothreitol or the antioxidant N-acetylcysteine. In conclusion, we describe two different causes of fatigue-induced prolonged low-frequency force depression, which correlate to differences in SOD activity and ROS metabolism. These findings may have clinical implications since ROS-mediated impairments in myofibrillar function can be counteracted by reductants and antioxidants, whereas changes in SR Ca(2+) handling appear more resistant to interventions.

Chemical energetics of force development, force maintenance, and relaxation in mammalian smooth muscle

PubMed Central

1980-01-01

High-energy phosphate utilization (delta approximately P) associated with force development, force maintenance, and relaxation has been determined during single isometric tetani in the rabbit taenia coli. ATP resynthesis from glycolysis and respiration was stopped without deleterious effects on the muscle. At 18 degrees C and a muscle length of 95% l0, the resting rate of energy utilization is 1.8 +/- 0.2 nmol/g . s-1, or 0.85 +/- 0.2 mmol approximately P/mol of total creatine (Ct) . s-1, where Ct = 2.7 mumol/g wet wt. During the initial 25 s of stimulation when force is developed, the average rate of delta approximately P was -8.2 +/- 0.8 mmol/mol Ct . s-1, some four times greater than during the subsequent 35 s of force maintenance, when the rate was -2.0 +/- 0.6 mmol approximately P/mol Ct . s-1. The energy cost of force redevelopment (0 to 95% P0) after a quick release from the peak of a tetanus is very low compared with the initial force development. Therefore, the high rate of energy utilization during force development is not due only to internal work done against the series elasticity nor to any high rate of cross-bridge cycling inherently associated with force development. The high economy of force maintenance compared with other muscle types is undoubtedly due to a slower cross-bridge cycle time. The energy utilization during 45 s of relaxation was not statistically significant, and integral of Pdt/delta approximately P was higher during relaxation than during force maintenance in the stimulated muscle. PMID:6969290

Microbial contamination of cosmetics and personal care items in Egypt--body lotions and talcum powders.

PubMed

Ashour, M S; Abdelaziz, A A; Hefni, H; el-Tayeb, O M

1989-06-01

We examined a total of 54 samples, including 18 body lotions and 36 talcum powders, for their total aerobic bacterial, coliform and fungal counts. We also carried out anaerobic bacterial counts for talcum powder as well as tests to detect some potentially hazardous bacteria in all tested samples. Talcum powders were more heavily contaminated with bacteria and fungi than body lotions. More than 40% of the tested body lotions contained no viable bacteria or less than 100 c.f.u./g. while all the talcum powders tested contained more than 100 c.f.u./g. Thirty per cent of the talcum powders were contaminated with 10(4) c.f.u./g. and none of the body lotions were contaminated to that extent. No coliforms were recovered from any of the body lotions, while 17% of the talcum powder examined contained coliforms in the range of 230-500 c.f.u./g. Staphylococcus spp. were detected in 18 samples of both talcum powders and body lotions, three of these Staphylococci were of the aureus type. Three samples of talcum powder contained E. coli, two samples contained Enterobacter agglomerans and one sample contained Citrobacter freundii. Seventy per cent of the body lotions showed no fungal counts, while 83% of the talcum powders examined were contaminated with fungi and most of the contaminated talcum powders contained more than 100 fungal cells/g. With regard to the anaerobic bacterial counts for talcum powders, 50% of the samples showed no counts while the other 50% contained less than 100 c.f.u./g. Four samples were contaminated with Clostridium perfringens, although C. tetani was not recovered from any of the samples.

Isotonic force modulates force redevelopment rate of intact frog muscle fibres: evidence for cross-bridge induced thin filament activation

PubMed Central

Vandenboom, Rene; Hannon, James D; Sieck, Gary C

2002-01-01

We tested the hypothesis that force-velocity history modulates thin filament activation, as assessed by the rate of force redevelopment after shortening (+dF/dtR). The influence of isotonic force on +dF/dtR was assessed by imposing uniform amplitude (2.55 to 2.15 μm sarcomere−1) but different speed releases to intact frog muscle fibres during fused tetani. Each release consisted of a contiguous ramp- and step-change in length. Ramp speed was changed from release to release to vary fibre shortening speed from 1.00 (2.76 ± 0.11 μm half-sarcomere−1 s−1) to 0.30 of maximum unloaded shortening velocity (Vu), thereby modulating isotonic force from 0 to 0.34 Fo, respectively. The step zeroed force and allowed the fibre to shorten unloaded for a brief period of time prior to force redevelopment. Although peak force redevelopment after different releases was similar, +dF/dtR increased by 81 ± 6% (P < 0.05) as fibre shortening speed was reduced from 1.00 Vu. The +dF/dtR after different releases was strongly correlated with the preceding isotonic force (r = 0.99, P < 0.001). Results from additional experiments showed that the slope of slack test plots produced by systematically increasing the step size that followed each ramp were similar. Thus, isotonic force did not influence Vu (mean: 2.84 ± 0.10 μm half-sarcomere−1 s−1, P < 0.05). We conclude that isotonic force modulates +dF/dtR independent of change in Vu, an outcome consistent with a cooperative influence of attached cross-bridges on thin filament activation that increases cross-bridge attachment rate without alteration to cross-bridge detachment rate. PMID:12205189

Skeletal muscle PLIN proteins, ATGL and CGI-58, interactions at rest and following stimulated contraction

PubMed Central

Ramos, Sofhia V.; Vandenboom, Rene; Roy, Brian D.; Peters, Sandra J.

2013-01-01

Evidence indicates that skeletal muscle lipid droplet-associated proteins (PLINs) regulate lipolysis through protein-protein interactions on the lipid droplet surface. In adipocytes, PLIN1 is thought to regulate lipolysis by directly interacting with comparative gene identification-58 (CGI-58), an activator of adipose triglyceride lipase (ATGL). Upon lipolytic stimulation, PLIN1 is phosphorylated, releasing CGI-58 to fully activate ATGL and initiate triglyceride breakdown. The absence of PLIN1 in skeletal muscle leads us to believe that other PLIN family members undertake this role. Our purpose was to examine interactions between PLIN2, PLIN3, and PLIN5, with ATGL and its coactivator CGI-58 at rest and following contraction. Isolated rat solei were incubated for 30 min at rest or during 30 min of intermittent tetanic stimulation [150-ms volleys at 60 Hz with a train rate of 20 tetani/min (25°C)] to maximally stimulate intramuscular lipid breakdown. Results show that the interaction between ATGL and CGI-58 increased 128% following contraction (P = 0.041). Further, ATGL interacts with PLIN2, PLIN3, and PLIN5 at rest and following contraction. The PLIN2-ATGL interaction decreased significantly by 21% following stimulation (P = 0.013). Both PLIN3 and PLIN5 coprecipitated with CGI-58 at rest and following contraction, while there was no detectable interaction between PLIN2 and CGI-58 in either condition. Therefore, our findings indicate that in skeletal muscle, during contraction-induced muscle lipolysis, ATGL and CGI-58 strongly associate and that the PLIN proteins work together to regulate lipolysis, in part, by preventing ATGL and CGI-58 interactions at rest. PMID:23408028

Injury and mortality of warmwater fishes immobilized by electrofishing

USGS Publications Warehouse

Dolan, C.R.; Miranda, L.E.

2004-01-01

Most studies of injury associated with electrofishing have focused on salmonids: few have given attention to warmwater fishes. Under controlled laboratory conditions, we treated bluegill Lepomis macrochirus, channel catfish Ictalurus punctatus, and largemouth bass Micropterus salmoides of various sizes to duty cycles ranging from 1.5% to 100%. This range of duty cycles represented continuous DC and pulsed-DC frequencies ranging from 15 to 110 Hz and pulse durations of 1 to 6 ms. At each duty cycle, fish were exposed to power densities in excess of those required to immobilize them within 3 s, and we subsequently determined the incidence of hemorrhage, spinal injury, and mortality. Incidence of hemorrhage averaged 3% (range, 0-25%), differed among species, and was not related to duty cycle or fish size. Incidence of spinal injury averaged 3% (range, 0-22%) and mortality averaged 10% (range, 0-75%); both differed among species and were related to duty cycle, fish size, and interactions among these variables. Largemouth bass was the species most vulnerable to hemorrhage, spinal injury, and mortality, channel catfish the least vulnerable; bluegills exhibited effects that were intermediate. Small centrarchids were especially susceptible to mortality. Fish tetanized by the electrical treatment were more likely to experience injury and mortality than fish that were only narcotized. However, mortality was not related to the injuries studied because hemorrhage and spinal injuries were similar in fish that survived electroshock and in those that died. We suggest that electrofishing with intermediate to high duty cycles could reduce electrofishing-induced injury and mortality to warmwater fish. Additionally, the power output and electrode system should be managed to induce narcosis and prevent tetany and to avoid the large peak powers required to immobilize small individuals.

Analysis of Electrocardiograms Associated with Pediatric Electrical Burns.

PubMed

McLeod, Jennifer S; Maringo, Alison E; Doyle, Patrick J; Vitale, Lisa; Klein, Justin D; Shanti, Christina M

2017-05-26

The purpose of this study was to examine the utility of electrocardiograms (EKGs) for low-risk, low-voltage pediatric electrical burn victims. A retrospective chart review was conducted on 86 pediatric patients who presented to the children's hospital between 2000 and 2015 after sustaining electrical burns. Variables included source and estimated voltage, extent of injuries, length of stay, high risk factors, and EKG results. High risk factors included estimated voltage > 1000 V, lightning, tetany, symptoms, loss of consciousness, or seizures. Statistical analyses were conducted. Average age was 5 years. Of those who sustained burns, 84.5% (n = 71/84) had second-degree burns ≤ 1% TBSA or less. Eleven patients had high risk factors, 12.9% (n = 11/85) and most had length of stay < 3 days (91.8%; n = 78/85). Majority sustained burns from low-voltage (< 300 V) household electrical outlets, cords, or light bulb sockets (90.4%; n = 75/83). Among patients with available EKGs, 12 had arrhythmias on initial EKG (i.e., low right atrial rhythm, t-wave inversions, sinus tachycardia, bundle branch block; 20.7%; n = 12/58). All were transient and nonfatal. The data suggest that low estimated voltage (< 300 V) electrical injuries were associated with negative EKGs; however, due to the low rate of arrhythmias, a Fisher's exact test did not show significance, P = 0.09 (P > 0.05). Preliminary data suggest that most pediatric electrical burns are due to low voltage (< 300 V) household sources. Few have high risk factors or arrhythmias that were transient and nonfatal. These data suggest that low-risk, asymptomatic, low-voltage pediatric electrical burns may not require an initial screening EKG.

Extracellular Ca2+-induced force restoration in K+-depressed skeletal muscle of the mouse involves an elevation of [K+]i: implications for fatigue

PubMed Central

Leader, John P.; Loiselle, Denis S.; Higgins, Amanda; Lin, Wei; Renaud, Jean-Marc

2015-01-01

We examined whether a Ca2+-K+ interaction was a potential mechanism operating during fatigue with repeated tetani in isolated mouse muscles. Raising the extracellular Ca2+ concentration ([Ca2+]o) from 1.3 to 10 mM in K+-depressed slow-twitch soleus and/or fast-twitch extensor digitorum longus muscles caused the following: 1) increase of intracellular K+ activity by 20–60 mM (raised intracellular K+ content, unchanged intracellular fluid volume), so that the K+-equilibrium potential increased by ∼10 mV and resting membrane potential repolarized by 5–10 mV; 2) large restoration of action potential amplitude (16–54 mV); 3) considerable recovery of excitable fibers (∼50% total); and 4) restoration of peak force with the peak tetanic force-extracellular K+ concentration ([K+]o) relationship shifting rightward toward higher [K+]o. Double-sigmoid curve-fitting to fatigue profiles (125 Hz for 500 ms, every second for 100 s) showed that prior exposure to raised [K+]o (7 mM) increased, whereas lowered [K+]o (2 mM) decreased, the rate and extent of force loss during the late phase of fatigue (second sigmoid) in soleus, hence implying a K+ dependence for late fatigue. Prior exposure to 10 mM [Ca2+]o slowed late fatigue in both muscle types, but was without effect on the extent of fatigue. These combined findings support our notion that a Ca2+-K+ interaction is plausible during severe fatigue in both muscle types. We speculate that a diminished transsarcolemmal K+ gradient and lowered [Ca2+]o contribute to late fatigue through reduced action potential amplitude and excitability. The raised [Ca2+]o-induced slowing of fatigue is likely to be mediated by a higher intracellular K+ activity, which prolongs the time before stimulation-induced K+ efflux depolarizes the sarcolemma sufficiently to interfere with action potentials. PMID:25571990

ROS-mediated decline in maximum Ca2+-activated force in rat skeletal muscle fibers following in vitro and in vivo stimulation.

PubMed

Dutka, Travis L; Verburg, Esther; Larkins, Noni; Hortemo, Kristin H; Lunde, Per K; Sejersted, Ole M; Lamb, Graham D

2012-01-01

We hypothesised that normal skeletal muscle stimulated intensely either in vitro or in situ would exhibit reactive oxygen species (ROS)-mediated contractile apparatus changes common to many pathophysiological conditions. Isolated soleus (SOL) and extensor digitorum longus (EDL) muscles of the rat were bubbled with 95% O(2) and stimulated in vitro at 31°C to give isometric tetani (50 Hz for 0.5 s every 2 s) until maximum force declined to ≤30%. Skinned superficial slow-twitch fibers from the SOL muscles displayed a large reduction (∼41%) in maximum Ca(2+)-activated specific force (F(max)), with Ca(2+)-sensitivity unchanged. Fibers from EDL muscles were less affected. The decrease in F(max) in SOL fibers was evidently due to oxidation effects on cysteine residues because it was reversed if the reducing agent DTT was applied prior to activating the fiber. The GSH:GSSG ratio was ∼3-fold lower in the cytoplasm of superficial fibers from stimulated muscle compared to control, confirming increased oxidant levels. The presence of Tempol and L-NAME during in vitro stimulation prevented reduction in F(max). Skinned fibers from SOL muscles stimulated in vivo at 37°C with intact blood supply also displayed reduction in F(max), though to a much smaller extent (∼12%). Thus, fibers from muscles stimulated even with putatively adequate O(2) supply display a reversible oxidation-induced decrease in F(max) without change in Ca(2+)-sensitivity, consistent with action of peroxynitrite (or possibly superoxide) on cysteine residues of the contractile apparatus. Significantly, the changes closely resemble the contractile deficits observed in a range of pathophysiological conditions. These findings highlight how readily muscle experiences ROS-related deficits, and also point to potential difficulties when defining muscle performance and fatigue.

ROS-Mediated Decline in Maximum Ca2+-Activated Force in Rat Skeletal Muscle Fibers following In Vitro and In Vivo Stimulation

PubMed Central

Dutka, Travis L.; Verburg, Esther; Larkins, Noni; Hortemo, Kristin H.; Lunde, Per K.; Sejersted, Ole M.; Lamb, Graham D.

2012-01-01

We hypothesised that normal skeletal muscle stimulated intensely either in vitro or in situ would exhibit reactive oxygen species (ROS)-mediated contractile apparatus changes common to many pathophysiological conditions. Isolated soleus (SOL) and extensor digitorum longus (EDL) muscles of the rat were bubbled with 95% O2 and stimulated in vitro at 31°C to give isometric tetani (50 Hz for 0.5 s every 2 s) until maximum force declined to ≤30%. Skinned superficial slow-twitch fibers from the SOL muscles displayed a large reduction (∼41%) in maximum Ca2+-activated specific force (Fmax), with Ca2+-sensitivity unchanged. Fibers from EDL muscles were less affected. The decrease in Fmax in SOL fibers was evidently due to oxidation effects on cysteine residues because it was reversed if the reducing agent DTT was applied prior to activating the fiber. The GSH∶GSSG ratio was ∼3-fold lower in the cytoplasm of superficial fibers from stimulated muscle compared to control, confirming increased oxidant levels. The presence of Tempol and L-NAME during in vitro stimulation prevented reduction in Fmax. Skinned fibers from SOL muscles stimulated in vivo at 37°C with intact blood supply also displayed reduction in Fmax, though to a much smaller extent (∼12%). Thus, fibers from muscles stimulated even with putatively adequate O2 supply display a reversible oxidation-induced decrease in Fmax without change in Ca2+-sensitivity, consistent with action of peroxynitrite (or possibly superoxide) on cysteine residues of the contractile apparatus. Significantly, the changes closely resemble the contractile deficits observed in a range of pathophysiological conditions. These findings highlight how readily muscle experiences ROS-related deficits, and also point to potential difficulties when defining muscle performance and fatigue. PMID:22629297

Confocal imaging of transmembrane voltage by SEER of di-8-ANEPPS

PubMed Central

Manno, Carlo; Figueroa, Lourdes; Fitts, Robert

2013-01-01

Imaging, optical mapping, and optical multisite recording of transmembrane potential (Vm) are essential for studying excitable cells and systems. The naphthylstyryl voltage-sensitive dyes, including di-8-ANEPPS, shift both their fluorescence excitation and emission spectra upon changes in Vm. Accordingly, they have been used for monitoring Vm in nonratioing and both emission and excitation ratioing modes. Their changes in fluorescence are usually much less than 10% per 100 mV. Conventional ratioing increases sensitivity to between 3 and 15% per 100 mV. Low sensitivity limits the value of these dyes, especially when imaged with low light systems like confocal scanners. Here we demonstrate the improvement afforded by shifted excitation and emission ratioing (SEER) as applied to imaging membrane potential in flexor digitorum brevis muscle fibers of adult mice. SEER—the ratioing of two images of fluorescence, obtained with different excitation wavelengths in different emission bands—was implemented in two commercial confocal systems. A conventional pinhole scanner, affording optimal setting of emission bands but less than ideal excitation wavelengths, achieved a sensitivity of up to 27% per 100 mV, nearly doubling the value found by conventional ratioing of the same data. A better pair of excitation lights should increase the sensitivity further, to 35% per 100 mV. The maximum acquisition rate with this system was 1 kHz. A fast “slit scanner” increased the effective rate to 8 kHz, but sensitivity was lower. In its high-sensitivity implementation, the technique demonstrated progressive deterioration of action potentials upon fatiguing tetani induced by stimulation patterns at >40 Hz, thereby identifying action potential decay as a contributor to fatigue onset. Using the fast implementation, we could image for the first time an action potential simultaneously at multiple locations along the t-tubule system. These images resolved the radially varying lag associated with propagation at a finite velocity. PMID:23440278

A Case of Vitamin D-Dependent Rickets Type 1A with a Novel Mutation in the Uzbek Population.

PubMed

Özcabı, Bahar; Tahmiscioğlu Bucak, Feride; Jaferova, Sevinç; Oruç, Çiğdem; Adrovic, Amra; Ceylaner, Serdar; Ercan, Oya; Evliyaoğlu, Olcay

2016-12-01

Vitamin D-dependent rickets type 1A (VDDR-1A) (Online Mendelian Inheritance in Man #264700) is a rare, autosomal recessively inherited disorder due to inactivating mutations in CYP27B1. It is characterized by early onset of rickets with hypocalcemia. We aimed to describe the clinical and laboratory findings in a VDDR-1A case and to report a novel homozygote truncating mutation NM_000785.3 c.403C>T (p.Q135*) in CYP27B1 which to our knowledge is the first described mutation in the Uzbek population. The patient was admitted with tetany at the age of 12 months. He was a healthy Uzbek boy until 9 months of age when he had a seizure due to hypocalcemia. Vitamin D treatment was given orally in Turkmenistan (no data available for dose and duration). The patient was the product of a consanguineous marriage. His brother had died with hypocalcemia and pneumonia. At physical examination, anthropometric measurements were within normal limits; he had caput quadratum, enlarged wrists, and carpopedal spasm. Blood calcium, phosphorus, alkaline phosphatase, and parathormone (PTH) levels were 5.9 mg/dL, 3.5 mg/dL, 987 IU/L, and 182.8 pg/mL (12-72), respectively. Radiological findings included cupping and fraying of the radial and ulnar metaphyses. Renal ultrasound revealed nephrocalcinosis (grade 1). Despite high serum PTH and 25-hydroxyvitamin D3 levels, 1,25-dihydroxyvitamin D3 level was low, suggesting a diagnosis of VDDR-1A. The patient was treated with calcium carbonate and calcitriol. DNA sequencing revealed a novel homozygous mutation of NM_000785.3 c.403C>T (p.Q135*) in CYP27B1. VDDR-1A is a rare disorder which needs to be considered even in countries where nutritional vitamin D deficiency is still common.

Evaluation of CP Chromo Select Agar for the enumeration of Clostridium perfringens from water.

PubMed

Manafi, Mammad; Waldherr, Kerstin; Kundi, Michael

2013-10-01

The European Directive on drinking water quality has included mCP agar as the reference method for recovering Clostridium perfringens from drinking waters. In the present study, three media (mCP, TSCF and CP Chromo Select Agar) were evaluated for recovery of C. perfringens in different surface water samples. Out of 139 water samples, using a membrane filtration technique, 131 samples (94.2%) were found to be presumptively positive for C. perfringens in at least one of the culture media. Green colored colonies on CP Chromo Select Agar (CCP agar) were counted as presumptive C. perfringens isolates. Out of 483 green colonies on CCP agar, 96.3% (465 strains, indole negative) were identified as C. perfringens, and 15 strains (3.1%) were indole positive and were identified as Clostridium sordellii, Clostridium bifermentans or Clostridium tetani. Only 3 strains (0.6%) gave false positive results and were identified as Clostridium fallax, Clostridium botulinum, and Clostridium tertium. Variance analysis of the data obtained shows statistically no significant differences in the counts obtained between media employed in this work. The mCP method is very onerous for routine screening and bacterial colonies could not be used for further biochemical testing. The colonies on CCP and TSCF were easy to count and subculture for confirmation tests. TSCF detects sulfite-reducing clostridia, including species other than C. perfringens, and in some cases excessive blackening of the agar frustrated counting of the colonies. If the contamination was too high, TSCF did not consistently produce black colonies and as a consequence, the colonies were white and gave false negative results. On the other hand, the identification of typical and atypical colonies isolated from all media demonstrated that CCP agar was the most useful medium for C. perfringens recovery in water samples. Copyright © 2013 Elsevier B.V. All rights reserved.

Confocal imaging of transmembrane voltage by SEER of di-8-ANEPPS.

PubMed

Manno, Carlo; Figueroa, Lourdes; Fitts, Robert; Ríos, Eduardo

2013-03-01

Imaging, optical mapping, and optical multisite recording of transmembrane potential (V(m)) are essential for studying excitable cells and systems. The naphthylstyryl voltage-sensitive dyes, including di-8-ANEPPS, shift both their fluorescence excitation and emission spectra upon changes in V(m). Accordingly, they have been used for monitoring V(m) in nonratioing and both emission and excitation ratioing modes. Their changes in fluorescence are usually much less than 10% per 100 mV. Conventional ratioing increases sensitivity to between 3 and 15% per 100 mV. Low sensitivity limits the value of these dyes, especially when imaged with low light systems like confocal scanners. Here we demonstrate the improvement afforded by shifted excitation and emission ratioing (SEER) as applied to imaging membrane potential in flexor digitorum brevis muscle fibers of adult mice. SEER--the ratioing of two images of fluorescence, obtained with different excitation wavelengths in different emission bands-was implemented in two commercial confocal systems. A conventional pinhole scanner, affording optimal setting of emission bands but less than ideal excitation wavelengths, achieved a sensitivity of up to 27% per 100 mV, nearly doubling the value found by conventional ratioing of the same data. A better pair of excitation lights should increase the sensitivity further, to 35% per 100 mV. The maximum acquisition rate with this system was 1 kHz. A fast "slit scanner" increased the effective rate to 8 kHz, but sensitivity was lower. In its high-sensitivity implementation, the technique demonstrated progressive deterioration of action potentials upon fatiguing tetani induced by stimulation patterns at >40 Hz, thereby identifying action potential decay as a contributor to fatigue onset. Using the fast implementation, we could image for the first time an action potential simultaneously at multiple locations along the t-tubule system. These images resolved the radially varying lag associated with propagation at a finite velocity.

Hyperparathyroidism in pregnancy: options for localization and surgical therapy.

PubMed

McMullen, Todd P W; Learoyd, Diana L; Williams, David C; Sywak, Mark S; Sidhu, Stan B; Delbridge, Leigh W

2010-08-01

Hyperparathyroidism in pregnancy is a threat to the health of both mother and fetus. The mothers suffer commonly from nephrolithiasis, hyperemesis, or even hypercalcemic crisis. Untreated disease will commonly complicate fetal development and fetal death is a significant risk. Treatment options, including medical and surgical therapy, are debated in the literature. This is a case series comprising seven patients with primary hyperparathyroidism in pregnancy. Data collected included symptoms at diagnosis, biochemical abnormalities, pathologic findings, treatment regimes, and subsequent maternal and fetal outcomes. Seven women, aged 20 to 39 years, presented with hyperparathyroidism during pregnancy. The earliest presented at 8 weeks and the latest at 38 weeks. Four of seven patients experienced renal calculi. Calcium levels were 2.7-3.5 mmol/l. All were found to have solitary parathyroid adenomas, of which two were in ectopic locations. Fetal complications included three preterm deliveries and one fetal death with no cases of neonatal tetany. Maternal and fetal complications could not be predicted based on duration or severity of hypercalcemia. Three patients were treated during pregnancy with surgery, and two of these had ectopic glands that required reoperations with a novel approach using Tc-99m sestamibi scanning during pregnancy to assist in localizing the abnormal gland. Four cases were treated postpartum with a combination of open and minimally invasive approaches after localization. No operative complications or fetal loss related to surgery were observed in this cohort. Primary hyperparathyroidism in pregnancy represents a significant risk for maternal and fetal complications that cannot be predicted by duration of symptoms or serum calcium levels. Surgical treatment should be considered early, and a minimally invasive approach with ultrasound is best suited to mitigating risk to mother and fetus. Equally important, Tc-99m sestamibi imaging may be used safely for localization of the parathyroids after negative cervical explorations.

Mitochondrial and myoplasmic [Ca2+] in single fibres from mouse limb muscles during repeated tetanic contractions

PubMed Central

Bruton, Joseph; Tavi, Pasi; Aydin, Jan; Westerblad, Håkan; Lännergren, Jan

2003-01-01

Previous studies on single fast-twitch fibres from mouse toe muscles have shown marked fatigue-induced changes in the free myoplasmic [Ca2+] ([Ca2+]i), while mitochondrial [Ca2+] remained unchanged. We have now investigated whether muscle fibres from the legs of mice respond in a similar way. Intact, single fibres were dissected from the soleus and extensor digitorum longus (EDL) muscles of adult mice. To measure [Ca2+]i, indo-1 was injected into the isolated fibres. Mitochondrial [Ca2+] was measured using Rhod-2 and confocal laser microscopy. Fatigue was induced by up to 1000 tetanic contractions (70 Hz) given at 2 s intervals. In soleus fibres, there was no significant decrease in tetanic [Ca2+]i at the end of the fatiguing stimulation, whereas tetanic force was significantly reduced by about 30 %. In 10 out of 14 soleus fibres loaded with Rhod-2 and subjected to fatigue, mitochondrial [Ca2+] increased to a maximum after about 50 tetani; this increase was fully reversed within 20 min after the end of stimulation. The force-frequency curve of the non-responding soleus fibres was shifted to higher frequencies compared to that of the responding fibres. In addition, eight out of nine Rhod-2-loaded EDL fibres showed similar changes in mitochondrial [Ca2+] during and after a period of fatiguing stimulation. The stimulation-induced increase in mitochondrial [Ca2+] was reduced when mitochondria were depolarised by application of carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone, whereas it was increased by application of an inhibitor of the mitochondrial Na+/Ca2+ exchange (CGP-37157). In conclusion, isolated slow-twitch muscle fibres show only modest changes in tetanic force and [Ca2+]i during repeated contractions. The increase in mitochondrial Ca2+ does not appear to be essential for activation of mitochondrial ATP production, nor does it cause muscle damage. PMID:12815178

Celiac disease and celiac crisis in children.

PubMed

Babar, Masud Iqbal; Ahmad, Irfan; Rao, Muhammad Suleman; Iqbal, Raghib; Asghar, Shakeel; Saleem, Mazhar

2011-08-01

To determine the frequency of clinical features of Celiac disease (CD) and Celiac crisis in children. Case series. Paediatrics Unit, Sheikh Zayed Medical College and Hospital, Rahim Yar Khan, from September 2009 to September 2010. Forty children aged between 4 to 13 years of either gender, presenting with complaints of recurrent diarrhea, abdominal distention, severe emaciation and dehydration were included. The information about breast feeding, weaning diets, age of introduction of wheat diets, onset of diarrhea, characteristics and frequency of stools, growth, vaccination status, symptoms in 1st degree relatives, restriction of Gluten diet in the past and anthropometric measures were recorded. Serological tests against anti-Tissue Transglultaminase (anti-tTG) antibodies were obtained in all cases. Upper gastrointestinal endoscopies were performed and multiple biopsies were taken from distal parts of duodenum. Among the forty children, twenty four (60%) were females and 16 were males (40%). The mean age was 6.35 ± 2.83 years. Thirty five (87.5%) parents were cousins. Breast feeding was not exclusively given and the Gluten containing weaning diets were given as early as 3.5 months of age. Thirty (75%) children presented with typical sign and symptoms of CD. Celiac crisis presented with profuse diarrhea, severe dehydration; abdominal distention; pedal edema, carpopedal spasm due to tetany; wasted muscles; head drop and inability to stand. The serum TtG antibodies in thirty-eight cases (95%) were above the cut off level of 7 u/ml ranging from 35-99 u/ml. The histopathology of specimens from distal duodenum revealed lesions of M3 type in thirteen (32.5%) and M2 type in eighteen cases (45%). All cases recovered and improved on follow-up after strict adherence to gluten-free diet (GFD). Majority of children with Celiac disease presented with typical symptom, while Celiac crisis was characterized by severe dehydration, weakness and calcium deficiency signs. Most were the product of consanguineous marriages and were given Gluten-containing weaning foods as early as the 4th month of life.

Design and construction of immune phage antibody library against Tetanus neurotoxin: Production of single chain antibody fragments.

PubMed

Sadreddini, Sanam; Seifi-Najmi, Mehrnosh; Ghasemi, Babollah; Kafil, Hossein Samadi; Alinejad, Vahideh; Sadreddini, Sevil; Younesi, Vahid; Jadidi-Niaragh, Farhad; Yousefi, Mehdi

2015-12-23

Tetanus neurotoxin (TeNT) is composed of a light (LC) and heavy chain (HC) polypeptides, released by anaerobic bacterium Clostridium tetani and can cause fatal life-threatening infectious disease. Toxin HC and LC modules represents receptor binding and zinc metalloprotease activity, respectively. The passive administration of animal-derived antibodies against tetanus toxin has been considered as the mainstay therapy for years. However, this treatment is associated with several adverse effects due to the presence of anti-isotype antibodies. In the present study, we have produced the fully human single chain antibody fragments (HuScFv) from two human antibody phage display libraries. Twenty-four different HuscFvs were isolated from two anti TeNT immune libraries. Our produced human ScFv (HuScFv) were converted to IgG platform and analyzed regarding their specific reactivity to TeNT. All of the selected scFvs have the same VL but different VH. Three HuscFvs from the first library (TTX15, 51, 75) and two HuscFvs from the second library (TTX16, 20) were chosen to convert to IgG1 using pOptiVEC and pcDNA3.3 systems. Production of IgG1 from transfected DG44 and binding capacity of them to tetanus toxin and toxoid were measured by ELISA. ELISA results showed no detectable production of TTX16 and TTX20 IgG1. Although, TTX51 and TTX75 were converted and produced as IgG1, no reactivity to tetanus toxin and toxoid was observed. However, TTX15 was successfully produced as whole IgG1 platform with reactivity to both tetanus toxin and toxoid. The latter would be an appropriate replacement for conventional polyclonal antibodies if would meet the further characterization including specificity determination, affinity measurement and toxin neutralizing assays. Our results demonstrated production of functional IgG1 derived from TTX15 scFv and might be an appropriate replacement for polyclonal Tetabulin but it needs further characterization.

Effects of presynaptic muscarinic cholinoreceptor blockade on neuromuscular transmission as assessed by the train-of-four and the tetanic fade response to rocuronium.

PubMed

Kim, Yong Beom; Lee, Sangseok; Lee, Kyeong Chun; Kim, Ha Jung; Ro, Young Jin; Yang, Hong-Seuk

2017-07-01

This study investigated the effect of muscarinic M 1 and M 2 receptor antagonists on the rocuronium-induced train of four (TOF) fade and tetanic fade, respectively. Ex-vivo phrenic nerves and diaphragms were obtained from adult Sprague-Dawley rats and stabilized in Krebs buffer; the nerve-stimulated muscle TOF fade was observed at 20 s intervals. For the TOF study, phrenic nerves and diaphragms were incubated with pirenzepine (an M 1 blocker) at concentrations of 0 nmol L -1 (control), 10 nmol L -1 (PZP10), or 100 nmol L -1 (PZP100). Rocuronium was then administered incrementally until the first twitch tension had depressed by >95% during TOF stimulation. The mean TOF ratios were compared when the first twitch tensions were depressed by 40%-50%. For the tetanic fade study, 50 Hz/5 s tetani was applied initially, 30 min after the administration of a loading dose of rocuronium and methoctramine (an M 2 receptor blocker, loaded at 0 μmol L -1 [control], 1 μmol L -1 [MET1], or 10 μmol L -1 [MET10]). The EC 95 of rocuronium was significantly lower in the PZP10 group than in the control group. In the PZP10 group, the TOF ratios at 50% and first twitch tension depression were significantly lower than those in the control group (P=.02). During tetanic stimulation, the tetanic fade was significantly enhanced in the MET10 group compared to the other groups. This study shows that antagonists of muscarinic M 1 and M 2 receptors affect the rocuronium-induced neuromuscular block as demonstrated by the reduced EC 95 and TOF ratios (M 1 antagonist, pirenzepine) or the enhanced 50-Hz tetanic fade (M 2 antagonist, methoctramine). © 2017 The Authors. Clinical and Experimental Pharmacology and Physiology Published by John Wiley & Sons Australia, Ltd.

Neonatal tetanus elimination in Pakistan: progress and challenges.

PubMed

Lambo, Jonathan A; Nagulesapillai, Tharsiya

2012-12-01

Pakistan is one of the 34 countries that have not achieved the neonatal tetanus (NT) global elimination target set by the World Health Organization (WHO). NT, caused by Clostridium tetani, is a highly fatal infection of the neonatal period. It is one of the most underreported diseases and remains a major but preventable cause of neonatal and infant mortality in many developing countries. In 1989, the World Health Assembly called for the elimination of NT by 1995, and since then considerable progress has been made using the following strategies: clean delivery practices, routine tetanus toxoid (TT) immunization of pregnant women, and immunization of all women of childbearing age with three doses of TT vaccine in high-risk areas during supplementary immunization campaigns. This review presents the activities, progress, and challenges in achieving NT elimination in Pakistan. A review of the literature found TT vaccination coverage in Pakistan ranged from 60% to 74% over the last decade. Low vaccination coverage, the main driver for NT in Pakistan, is due to many factors, including demand failure for TT vaccine resulting from inadequate knowledge of TT vaccine among reproductive age females and inadequate information about the benefits of TT provided by health care workers and the media. Other factors linked to low vaccination coverage include residing in rural areas, lack of formal education, poor knowledge about place and time to get vaccinated, and lack of awareness about the importance of vaccination. A disparity exists in TT vaccination coverage and antenatal care between urban and rural areas due to access and utilization of health care services. NT reporting is incomplete, as cases from the private sector and rural areas are underreported. To successfully eliminate NT, women of reproductive age must be made aware of the benefits of TT vaccine, not only to themselves, but also to their families. Effective communication strategies for TT vaccine delivery and health education focusing on increasing awareness of NT are strongly suggested. It is imperative that the private and government sectors work cooperatively to report NT cases and improve routine TT vaccination coverage. Copyright © 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

The rhizome of Gastrodia elata Blume - An ethnopharmacological review.

PubMed

Zhan, Hong-Dan; Zhou, Hai-Yu; Sui, Yun-Peng; Du, Xin-Liang; Wang, Wei-Hao; Dai, Li; Sui, Feng; Huo, Hai-Ru; Jiang, Ting-Liang

2016-08-02

Gastrodia elata Blume (Orchidaceae) is commonly called Tian ma in Chinese and mainly distributed in the mountainous areas of eastern Asia, such as China, Korea, Japan and India. It is an extensively used traditional Chinese herbal medicine in the clinical practice of traditional Chinese medicine, to treat headache, migraine, dizziness, epilepsy, infantile convulsion, tetany and so on. The present paper reviews the advancements in investigation of botany and ethnopharmacology, phytochemistry, pharmacology, toxicology and quality control of Gastrodia elata Blume. Finally, the possible tendency and perspective for future investigation of this plant are also put forward. The information on Gastrodia elata Blume was collected via piles of resources including classic books about Chinese herbal medicine, and scientific databases including Pubmed, Google Scholar, ACS, Web of science, ScienceDirect databases, CNKI and others. Plant taxonomy was validated by the databases "The Plant List", and "Mansfeld's Encyclopedia". Over 81 compounds from this plant have been isolated and identified, phenolics and polysaccharides are generally considered as the characteristic and active constituents of Gastrodia elata Blume. Its active compounds possess wide-reaching biological activities, including sedative, hypnotic, antiepileptic, anticonvulsive, antianxietic, antidepressant, neuroprotective, antipsychotic, anti-vertigo, circulatory system modulating, anti-inflammationary, analgesic, antioxidative, memory-improving and antiaging, antivirus and antitumor effects. Despite the publication of various papers on Gastrodia elata Blume, there is still, however, the need for definitive research and clarification of other bioactive compounds using bioactivity-guided isolation strategies, and the possible mechanism of action as well as potential synergistic or antagonistic effects of multi-component mixtures derived from Gastrodia elata Blume need to be evaluated. It is also necessary and important to do more quality control and toxicological study on human subjects in order to maintain its efficacy stable in the body and validate its safety in clinical uses. In addition, more investigations on other parts of this plant beyond the tubers are needed. Further studies on Gastrodia elata Blume will lead to the development of new drugs and therapeutics for various diseases, and how to utilize it better should be paid more attention to. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Certain applied electrical signals during EPG cause negative effects on stylet probing behaviors by adult Lygus lineolaris (Hemiptera: Miridae).

PubMed

Backus, Elaine A; Cervantes, Felix A; Godfrey, Larry; Akbar, Waseem; Clark, Thomas L; Rojas, Maria G

This study is the first to fully evaluate whether electrical signals applied to large insects during electropenetrography (EPG; also called electrical penetration graph) negatively affect insect behavior. During EPG, electrical signals are applied to plants, and thus to the gold-wire-tethered insects feeding on them. The insect completes an electrical circuit whose changes in voltage reflect the insect's stylet probing/penetration behaviors, recorded as waveform output. For nearly 50 years of EPG science, evidence has supported that there are no or negligible effects on tiny insects from applied electricity during EPG. Recently however, EPG studies of large-bodied hemipterans such as heteropterans and sharpshooter leafhoppers have been published. The wider stylet diameters of such large insects cause them to have lower inherent resistances to applied signals compared with smaller insects, conveying more electrical current. The present study asked whether such increased currents would affect insect stylet probing, by comparing Lygus lineolaris behaviors on pin-head cotton squares using an AC-DC electropenetrograph. Effects of AC or DC applied signals were separately examined in two factorial studies, each comparing four input resistor (Ri) levels (10 6 , 10 7 , 10 8 and 10 9  Ω) and four applied voltage levels (2, 60, 150 and 250 mV). Results showed that changes in both probing and non-probing behaviors were indeed caused by changing signal type, Ri level, or applied voltage. Negative effects on feeding were numerically greater overall for DC than AC applied signals, perhaps due to muscular tetany from DC; however, AC versus DC could not be statistically tested. Results strongly support the need for flexible Ri and applied voltage levels and types, to tailor instrument settings to the size and special needs of each insect subject. Our findings will facilitate further EPG studies of Lygus spp., such as host plant resistance or insecticidal assays/bioassays to assess mode of action and appropriate dosage. It is hoped that this study will also inform EPG studies of similar, large heteropterans in the future. Published by Elsevier Ltd.

A rapid qualitative assay for detection of Clostridium perfringens in canned food products.

PubMed

Dave, Gayatri Ashwinkumar

2017-01-01

Clostridium perfringens (MTCC 1349) is a Gram-positive, anaerobic, endospore forming, and rod-shaped bacterium. This bacterium produces a variety of toxins under strict anaerobic environment. C. perfringens can grow at temperatures ranging between 20°C and 50°C. It is the major causetive agent for gas gangrene, cellulitis, septicemia, necrotic enteritis and food poisoning, which are common toxin induced conditions noted in human and animals. C. perfringens can produce produce four major types of toxins that are used for the classification of strains, classified under type A-E. Across the globe many countries, including the United States, are affected by C. perfringens food poisonings where it is ranked as one of the most common causes of food borne infections. To date, no direct one step assay for the detection of C. perfringens has been developed and only few methods are known for accurate detection of C. perfringens. Long detection and incubation time is the major consideration of these reporter assays. The prensent study proposes a rapid and reliable colorimetric assay for the detection of C. perfringens. In principale, this assay detects the para nitrophenyl (yellow colour end product) liberated due to the hydrolysis of paranitrophenyl phosphetidyl choline (PNPC) through phospholipase C (lecithinase). Constitutive secretion of phospholipase C is a charactristic feature of C. perfringens. This assay detects the presence of the extracellular lecithinse through the PNPC impragnated impregnated probe. The probe is impregnated with peranitrophenyl phosphotidyl choline ester, which is colourless substrate used by lecithinase. The designed assay is specific towards PNPC and detectes very small quantites of lecithinase under conditions used. The reaction is substrate specific, no cross reaction was observed upon incubation with other substrates. In addition, this assay gave negative results with other clostridium strains, no cross reactions were observed with other experimental strains like C. tetani, C. botulinum, C. acetobutyricum, Bacillus subtilis, and Escherichia coli. This assay is extramly rapid and provides reliable and reproducible results within one hour of incubation at 37°C.

The role of frequency in the effects of long-term intermittent stimulation of denervated slow-twitch muscle in the rat.

PubMed Central

Al-Amood, W S; Lewis, D M

1987-01-01

1. Rat soleus muscle was denervated by sciatic transection and electrically stimulated for periods of between 3 and 9 weeks with intermittent 1 s bursts of pulses. Most of the bursts were either repeated every 90 s and pulses within them had frequencies between 10 and 100 Hz, or had a frequency of 50 Hz and were repeated at intervals between 60 and 600 s. Comparisons were made with continuous stimulation at 10 Hz. 2. At the end of the period of stimulation, isometric twitches and tetani were measured and, in a proportion, also isotonic shortening velocity. 3. Isometric twitch duration (contraction and relaxation) decreased with time of stimulation. Very similar effects were seen in all animals in which intermittent stimulation had been used. There was a significant relationship between the change in twitch duration and the frequency used within the bursts of chronic stimulation, with slightly larger effects at frequencies of 40 and 60 Hz. The lowest burst repetition rate produced the largest effects. 4. It was confirmed that similar changes were found in denervated muscles that were not stimulated, although these changes were smaller and developed more slowly. 5. The extreme loss of tetanic tension induced in the muscle by denervation was reduced by chronic stimulation, with no significant difference between different regimes, although there were small differences which showed the same patterns of effectiveness described for twitch durations. 6. Continuous stimulation at 10 Hz maintained the twitch contraction and relaxation phases at the values found 3 weeks after denervation, that is it prevented secondary shortening of the twitch. Continuous stimulation reduced tension loss but was, perhaps, less effective than intermittent stimulation. 7. Twitch-tetanus ratio increased with denervation with little spontaneous reversal later. Stimulation at all frequencies reduced the ratio, but it did not reach normal values. 8. Isotonic shortening velocity was measured in many of the muscles. Maximum velocity was estimated and normalized by muscle length.(ABSTRACT TRUNCATED AT 400 WORDS) Images Fig. 3 PMID:3446785

The effects of virtual reality-based bilateral arm training on hemiplegic children's upper limb motor skills.

PubMed

Do, Ji-Hye; Yoo, Eun-Young; Jung, Min-Ye; Park, Hae Yean

2016-01-01

Hemiplegic cerebral palsy is a neurological symptom appearing on the unilateral arm and leg of the body that causes affected upper/lower limb muscle weakening and dysesthesia and accompanies tetany and difficulties in postural control due to abnormal muscle tone, and difficulties in body coordination. The purpose of this study was to examine the impact of virtual reality-based bilateral arm training on the motor skills of children with hemiplegic cerebral palsy, in terms of their upper limb motor skills on the affected side, as well as their bilateral coordination ability. The research subjects were three children who were diagnosed with hemiplegic cerebral palsy. The research followed an ABA design, which was a single-subject experimental design. The procedure consisted of a total of 20 sessions, including four during the baseline period (A1), 12 during the intervention period (B), and four during the baseline regression period (A2), For the independent variable bilateral arm training based on virtual reality, Nintendo Wii game was played for 30 minutes in each of the 12 sessions. For the dependent variables of upper limb motor skills on the affected side and bilateral coordination ability, a Wolf Motor Function Test (WMFT) was carried out for each session and the Pediatric Motor Activity Log (PMAL) was measured before and after the intervention, as well as after the baseline regression period. To test bilateral coordination ability, shooting baskets in basketball with both hands and moving large light boxes were carried out under operational definitions, with the number of shots and time needed to move boxes measured. The results were presented using visual graphs and bar graphs. The study's results indicated that after virtual reality-based bilateral arm training, improvement occurred in upper limb motor skills on the affected sides, and in bilateral coordination ability, for all of the research subjects. Measurements of the effects of sustained therapy after completion of the intervention, during the baseline regression period, revealed that upper limb motor skills on the affected side and bilateral coordination ability were better than in the baseline period for all subjects. This study confirmed that for children with hemiplegic with cerebral palsy, bilateral arm training based on virtual reality can be an effective intervention method for enhancing the upper limb motor skills on the affected side, as well as bilateral coordination ability.

[Neurological disorders in patients with hypoparathyroidism].

PubMed

Roztoczyńska, Dorota; Kroczka, Sławomir; Kumorowicz-Czoch, Małgorzata; Dolezal-Ołtarzewska, Katarzyna; Kacińsk, Marek; Starzyk, Jerzy

2010-01-01

The term hypoparathyroidism refers to a group of disorders in which a relative or absolute deficiency of PTH leads to hypocalcemia and hyperphosphatemia. Was to evaluate clinical symptoms in patients with hypoparathyroidism during normocalcemic period and to try to establish its etiology (electrolyte imbalance, organic central nervous system lesions, coincidence of tetany and epilepsy). The analysis included a group of 14 patients with hypoparathyroidism: 3 boys and 11 girls, aged from 12 months to 31 years (median 16.11 years), with duration of the disease 12 months to 26 years (median 10.9 years). In all the patients, the diagnosis was confirmed based on history, physical examination, results of biochemical and hormonal laboratory tests, radiological and neurological examinations. All the patients were followed by endocrinology specialists. Low phosphorus diet, calcium, magnesium, active vitamin D supplementation and management of other endocrine disorders were employed. In 9 patients, pseudo-hypoparathyrodism was diagnosed; of this number, in 8 children, type Ia Albright syndrome was confirmed. Five patients were diagnosed as true hypoparathyroidism, two girls in this group were found to have autoimmune hypoparathyroidism as a component of the autoimmune polyglandular syndrome type 1, 2 others were diagnosed in infancy as congenital hypoparathyroidism and 1 girl had true hypoparathyroidism as a component of Kearns-Sayre syndrome. Five patients were referred to neurological department with epilepsy suspicion. In the medical history, 9 patients had generalized epileptic seizures, moreover, 1 girl manifested absence attack and balance disturbances. In 3 patients, EEG demonstrated changes typical of generalized seizure activity. In 5 patients on anti-epileptic management, additional calcium and active vitamin D treatment was initiated, allowing for achieving seizure remission. CT of the head and pituitary gland showed calcification foci in the central nervous system in 9 patients. Five patients of the eight individuals with Albright syndrome showed mild or moderate mental retardation confirmed by psychological testing. 1. Hypoparathyroidism leads to functional and morphological CNS changes. 2. Restoring metabolic balance through administration of calcium and active vitamin D preparations may obliterate the need for anti-epileptic treatment. 3. Calcification foci in the central nervous system seem to be associated with the duration of hypoparathyroidism. 4. No correlation has been observed between the extent and location of calcification foci and neurological abnormalities. 5. Hypoparathyroid patients with calcification foci in CSN require long-term multidisciplinary medical management and neurophysiological, imaging and neuropsychological monitoring.

Variable clinical spectrum of the most common inborn error of bile acid metabolism--3beta-hydroxy-Delta 5-C27-steroid dehydrogenase deficiency.

PubMed

Subramaniam, Pushpa; Clayton, Peter T; Portmann, Bernard C; Mieli-Vergani, Giorgina; Hadzić, Nedim

2010-01-01

We studied the clinical features of children with 3beta-hydroxy-Delta 5-C27-steroid dehydrogenase (3beta-HSDH) deficiency presenting to King's College and Great Ormond Street hospitals between 1989 and 2005. The diagnosis was made biochemically by detection of sulphated dihydroxycholenoic acids and trihydroxycholenoic acids in urine by fast atom bombardment mass spectrometry or electrospray ionisation tandem mass spectrophotometry and a plasma bile acid profile showing absent or low cholic and chenodeoxycholic acid levels and high concentrations of 3beta-7 alpha-dihydroxy-5-cholenoic acid and 3beta-7 alpha-12 alpha-trihydroxy-5-cholenoic acid. Eighteen children (12 male) with 3beta-HSDH deficiency were identified and diagnosed at a median age of 1.35 years (range 8 weeks-11 years). The presenting features included neonatal cholestasis (n = 11), rickets (n = 8, 1 of whom also had hypocalcaemic tetany, seizures, and normal liver biochemical markers), hepatomegaly (n = 7), pruritus (n = 3), and steatorrhoea and failure to thrive (n = 3). Ten children had low serum 25-OH vitamin D levels, of whom 8 also had low vitamin E and 6 had low vitamin A serum levels. Liver histology showed giant cell change and hepatocyte disarray in all with added features of cholestasis in 11, bridging fibrosis in 6, micronodular cirrhosis in 1, fatty change in 1, and active lobular and portal inflammation in 1. Five patients were treated with cholic acid and chenodeoxycholic acid (7 mg x kg(-1) x day(-1) of each), 7 with chenodeoxycholic acid only (7-18 mg x kg(-1) x day(-1)), and 1 with cholic acid (8 mg x kg(-1) x day(-1)) only. Repeated liver biopsies performed in 4 patients 6 months after starting replacement therapy showed improved histological changes. Three children died untreated before 5 years of age. After a median follow-up of 5.5 years (range 1-17 years) 12 out of 13 treated children have no clinical signs of liver disease or of fat-soluble vitamin deficiency. 3beta-HSDH deficiency is a rare inborn error of metabolism with diverse clinical features. Early replacement treatment leads to clinical and biochemical control and prevents chronic liver and bone disease, at least in the medium term.

Replacement of the in vivo neutralisation test for efficacy demonstration of tetanus vaccines ad us. vet.

PubMed

Rosskopf, Ute; Noeske, Kerstin; Werner, Esther

2005-01-01

The bacterium Clostridium (C.) tetani is an ubiquitous pathogen. This anaerobic, gram-positive bacterium can form spores and can be found in the whole environment. It enters the body via injuries of the skin and wounds where it releases the neurotoxin "tetanospasmin" (= tetanus toxin). The animals most susceptible to tetanus infection are horses and sheep. Only active immunisation by tetanus vaccine provides effective protection against tetanus intoxication. The marketing authorisation requirements stipulate that efficacy of tetanus vaccines ad us. vet. must be demonstrated in all target animal species via determination of neutralising tetanus serum antitoxin concentrations. The standard method used for this purpose is still the toxin neutralisation test (TNT), as it quantifies the tetanus toxin-neutralising effect of tetanus serum antibodies in vivo. In this test, tetanus toxin is added to dilutions of serum from vaccinated horse and sheep. The serum dilutions are then administered to mice or guinea pigs, which are observed for toxic symptoms. Against the background of animal protection, the goal of one project of the Paul-Ehrlich-Institut (Bundesministerium fuer Bildung und Forschung (Federal Ministry for Education and Research), 0312636) was to establish an alternative to the toxin neutralisation test, enabling the testing of efficacy of tetanus vaccines with serological in vitro methods. For this purpose, a so-called double antigen ELISA (DAE) was established which enables the testing of sera of different species in one assay. In addition, the sera were tested in an indirect ELISA for horses and sheep separately. Altogether, ten groups of horses and eight groups of sheep were immunised with ten animals per group each. The tetanus vaccines comprised almost all products authorised for the German market at the start of the project. 564 horse sera and 257 sheep sera were tested using the two ELISA methods. Some sera were also tested in vivo. The kinetics of antibody responses were recorded. The in vitro DAE method seems to be suitable to replace the mouse neutralisation test used for the detection of tetanus antitoxin in sera of target animal species. The comparison of some sera in the ELISA and the TNT showed good equivalence of results. Nevertheless, before an ELISA titre in horse and sheep sera indicating unambiguous protection against tetanus can be fixed, further comparative assays of low titre sera in the TNT and the DAE will have to be performed.

Clinical and genetic characteristics of Pseudohypoparathyroidism in the Chinese population.

PubMed

Chu, Xueying; Zhu, Yan; Wang, Ou; Nie, Min; Quan, Tingting; Xue, Yu; Wang, Wenbo; Jiang, Yan; Li, Mei; Xia, Weibo; Xing, Xiaoping

2018-02-01

Pseudohypoparathyroidism (PHP) is caused by mutations and epimutations in the GNAS locus, and characterized by the possibility of resistance to multiple hormones and Albright's hereditary osteodystrophy. PHP can be classified into the forms 1A/C, sporadic 1B and familial 1B. To obtain an overall view of the clinical and genetic characteristics of the Chinese PHP patient population. From 2000 to 2016, 120 patients were recruited and studied using Sanger sequencing, methylation-specific multiple ligation-dependent probe amplification (MS-MLPA) and combined bisulfite restriction analysis (COBRA). Of these patients, 104 had positive molecular alterations indicative of certain forms of PHP and were included in data analysis. Clinical and laboratory features were compared between PHP1A/C and PHP1B patients. Ten PHP1A/C, 21 familial PHP1B and 73 sporadic PHP1B patients were identified. Four novel GNAS mutations were discovered in these patients, including c.1038+1G>T, c.530+2T>C, c.880_883delCAAG and c.311_312delAAG, insT. The most common symptoms in this series were recurrent tetany (89.4%) and epilepsy (47.1%). The prevalence of weight excess increased with age for PHP1B (10%-35%) and PHP1A/C (50%-75%). Intracranial calcification had a prevalence of 94.6% and correlated with seizures (r = .227, P = .029). Cataracts occurred in 56.2% PHP patients, and there was a trend towards longer disease duration in patients with cataracts (P = .051). Statistically significant differences (P < .05) were observed when comparing certain clinical characteristics between PHP1B and PHP1A/C patients, including age of onset (10 vs 7 year), short stature (21.3% vs 70%), rounded face (60.6% vs 100%), brachydactyly (25.5% vs 100%), ectopic ossification (1.1% vs 40%) and TSH resistance (44.6% vs 90%), respectively. This study is the largest single-centre series of PHP patients and summarizes the clinical and genetic features of the Chinese PHP population. While there was substantial clinical overlap between PHP1A/C and PHP1B, differences in disease progression were observed. © 2017 John Wiley & Sons Ltd.

Effects of high-intensity swimming training on GLUT-4 and glucose transport activity in rat skeletal muscle.

PubMed

Terada, S; Yokozeki, T; Kawanaka, K; Ogawa, K; Higuchi, M; Ezaki, O; Tabata, I

2001-06-01

This study was performed to assess the effects of short-term, extremely high-intensity intermittent exercise training on the GLUT-4 content of rat skeletal muscle. Three- to four-week-old male Sprague-Dawley rats with an initial body weight ranging from 45 to 55 g were used for this study. These rats were randomly assigned to an 8-day period of high-intensity intermittent exercise training (HIT), relatively high-intensity intermittent prolonged exercise training (RHT), or low-intensity prolonged exercise training (LIT). Age-matched sedentary rats were used as a control. In the HIT group, the rats repeated fourteen 20-s swimming bouts with a weight equivalent to 14, 15, and 16% of body weight for the first 2, the next 4, and the last 2 days, respectively. Between exercise bouts, a 10-s pause was allowed. RHT consisted of five 17-min swimming bouts with a 3-min rest between bouts. During the first bout, the rat swam without weight, whereas during the following four bouts, the rat was attached to a weight equivalent to 4 and 5% of its body weight for the first 5 days and the following 3 days, respectively. Rats in the LIT group swam 6 h/day for 8 days in two 3-h bouts separated by 45 min of rest. In the first experiment, the HIT, LIT, and control rats were compared. GLUT-4 content in the epitrochlearis muscle in the HIT and LIT groups after training was significantly higher than that in the control rats by 83 and 91%, respectively. Furthermore, glucose transport activity, stimulated maximally by both insulin (2 mU/ml) (HIT: 48%, LIT: 75%) and contractions (25 10-s tetani) (HIT: 55%, LIT: 69%), was higher in the training groups than in the control rats. However, no significant differences in GLUT-4 content or in maximal glucose transport activity in response to both insulin and contractions were observed between the two training groups. The second experiment demonstrated that GLUT-4 content after HIT did not differ from that after RHT (66% higher in trained rats than in control). In conclusion, the present investigation demonstrated that 8 days of HIT lasting only 280 s elevated both GLUT-4 content and maximal glucose transport activity in rat skeletal muscle to a level similar to that attained after LIT, which has been considered a tool to increase GLUT-4 content maximally.

Primary hypoparathyroidism in dogs: a retrospective study of 17 cases.

PubMed

Russell, N J; Bond, K A; Robertson, I D; Parry, B W; Irwin, P J

2006-08-01

To evaluate the clinico-pathological findings, response to treatment and prevalence of complications in dogs with primary hypoparathyroidism. Retrospective study of 17 dogs presenting to the University of Melbourne Veterinary Clinical Centre and Murdoch University Veterinary Hospital over a 15 year period (1990 to 2004). Case records were evaluated for signalment, body weight, diet type, historical and clinical findings, serum total calcium, phosphate, albumin and parathyroid hormone concentrations, urinary fractional excretion ratios of calcium and phosphate, electrocardiogram (ECG) results, treatments administered, outcome and period of follow-up. The most common breeds identified were St Bernard (three dogs), Chihuahua (two dogs), German Shepherd (two dogs) and Jack Russell Terrier (two dogs). Three dogs were cross bred. Seizures, muscle tremors and fasciculations, stiff gait, tetany, muscle cramping, behavioural change and hyperventilation were the most common clinical signs. Vomiting, inappetence, diarrhoea, abdominal pain, hyperthermia, facial pruritus, ataxia, weakness, cataracts, and circling also occurred with less frequency. The mean duration of observed clinical signs preceding diagnosis was 33 days (median 13 days, range 1 to 173 days). All dogs had marked hypocalcaemia with normal or mildly increased serum albumin concentrations. Mean phosphate concentrations were significantly higher in inappetent dogs (P = 0.049). Mean serum calcium concentrations were significantly lower in dogs with cataracts compared to those without (P = 0.046). There were no other significant relationships between serum calcium or phosphate concentrations and the clinical presentation or outcome. No significant correlations were identified between the presence of a particular clinical sign and the duration of clinical signs. ECGs were obtained in four dogs and all exhibited QT interval prolongation due to a ST-segment prolongation. Sixteen of 17 dogs were treated successfully for hypocalcaemia and discharged from hospital. Acute management included parenteral calcium gluconate (10 dogs) and intravenous anticonvulsants (five dogs). Chronic therapy included oral vitamin D analogues and calcium supplementation. Treatment complications occurred in two dogs and included acute renal failure (one dog) and iatrogenic tissue necrosis following subcutaneous calcium administration (one dog). The mean follow-up period was 14.5 months (median 13 months, range 0 to 39 months). Twelve dogs were alive at the last follow up and two dogs were euthanased for unrelated reasons. The type of vitamin D analogue used was not associated with outcome. Primary hypoparathyroidism was an uncommon diagnosis in dogs. Saint Bernards, cross bred dogs, German Shepherd dogs and Terrier breeds were most commonly affected. Neurological signs were the most common presenting clinical signs, although alimentary signs may have been more common than previously reported. Dogs with primary hypoparathyroidism appeared to have a good prognosis following initiation of calcium supplementation and vitamin D therapy. Complications of treatment were uncommon and could be minimised with regular monitoring.

Vaccines for women to prevent neonatal tetanus.

PubMed

Demicheli, Vittorio; Barale, Antonella; Rivetti, Alessandro

2013-05-31

Tetanus is an acute, often fatal, disease caused by an exotoxin produced by Clostridium tetani. It occurs in newborn infants born to mothers who do not have sufficient circulating antibodies to protect the infant passively, by transplacental transfer. Prevention may be possible by the vaccination of pregnant or non-pregnant women, or both, with tetanus toxoid, and the provision of clean delivery services. Tetanus toxoid consists of a formaldehyde-treated toxin which stimulates the production of antitoxin. To assess the effectiveness of tetanus toxoid, administered to women of childbearing age or pregnant women, to prevent cases of, and deaths from, neonatal tetanus. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2012), The Cochrane Library (2012, Issue 10), PubMed (1966 to 31 October 2012), EMBASE (1974 to 31 October 2012). We also used the results from handsearching and consultations with manufacturers and authors. Randomised or quasi-randomised trials evaluating the effects of tetanus toxoid in pregnant women or women of childbearing age on numbers of neonatal tetanus cases and deaths. Three review authors independently assessed trials for inclusion and trial quality, and extracted data. Two trials (10,560 infants) were included. It should be noted that these trials are very old,1966 and 1980 respectively, and one trial randomised exclusively non-pregnant women. The main outcomes were measured on infants born to a subset of those randomised women who became pregnant during the course of the studies. One study (1919 infants) assessed the effectiveness of tetanus toxoid in comparison with influenza vaccine in preventing neonatal tetanus deaths. After a single dose, the risk ratio (RR) was 0.57 (95% confidence interval (CI) 0.26 to 1.24), and the vaccine effectiveness was 43%. With a two- or three-dose course, the RR was 0.02 (95% CI 0.00 to 0.30); vaccine effectiveness was 98%. No effect was detected on causes of death other than tetanus. The RR of cases of neonatal tetanus after at least one dose of tetanus toxoid was 0.20 (95% CI 0.10 to 0.40); vaccine effectiveness was 80%. Another study, involving 8641 children, assessed the effectiveness of tetanus-diptheria toxoid in comparison with cholera toxoid in preventing neonatal mortality after one or two doses. The RR was 0.68 (95% CI 0.56 to 0.82); vaccine effectiveness was 32%. In preventing deaths at four to 14 days, the RR was 0.38 (95% CI 0.27 to 0.55), and vaccine effectiveness 62% (95% CI 45% to 73%). Available evidence supports the implementation of immunisation practices on women of childbearing age or pregnant women in communities with similar, or higher, levels of risk of neonatal tetanus, to the two study sites. More information is needed on possible interference of vaccination by malaria chemoprophylaxis on the roles of malnutrition and vitamin A deficiency, and on the quality of tetanus toxoid production and storage.

Post-exercise recovery of contractile function and endurance in humans and mice is accelerated by heating and slowed by cooling skeletal muscle.

PubMed

Cheng, Arthur J; Willis, Sarah J; Zinner, Christoph; Chaillou, Thomas; Ivarsson, Niklas; Ørtenblad, Niels; Lanner, Johanna T; Holmberg, Hans-Christer; Westerblad, Håkan

2017-12-15

We investigated whether intramuscular temperature affects the acute recovery of exercise performance following fatigue-induced by endurance exercise. Mean power output was better preserved during an all-out arm-cycling exercise following a 2 h recovery period in which the upper arms were warmed to an intramuscular temperature of ̴ 38°C than when they were cooled to as low as 15°C, which suggested that recovery of exercise performance in humans is dependent on muscle temperature. Mechanisms underlying the temperature-dependent effect on recovery were studied in intact single mouse muscle fibres where we found that recovery of submaximal force and restoration of fatigue resistance was worsened by cooling (16-26°C) and improved by heating (36°C). Isolated whole mouse muscle experiments confirmed that cooling impaired muscle glycogen resynthesis. We conclude that skeletal muscle recovery from fatigue-induced by endurance exercise is impaired by cooling and improved by heating, due to changes in glycogen resynthesis rate. Manipulation of muscle temperature is believed to improve post-exercise recovery, with cooling being especially popular among athletes. However, it is unclear whether such temperature manipulations actually have positive effects. Accordingly, we studied the effect of muscle temperature on the acute recovery of force and fatigue resistance after endurance exercise. One hour of moderate-intensity arm cycling exercise in humans was followed by 2 h recovery in which the upper arms were either heated to 38°C, not treated (33°C), or cooled to ∼15°C. Fatigue resistance after the recovery period was assessed by performing 3 × 5 min sessions of all-out arm cycling at physiological temperature for all conditions (i.e. not heated or cooled). Power output during the all-out exercise was better maintained when muscles were heated during recovery, whereas cooling had the opposite effect. Mechanisms underlying the temperature-dependent effect on recovery were tested in mouse intact single muscle fibres, which were exposed to ∼12 min of glycogen-depleting fatiguing stimulation (350 ms tetani given at 10 s interval until force decreased to 30% of the starting force). Fibres were subsequently exposed to the same fatiguing stimulation protocol after 1-2 h of recovery at 16-36°C. Recovery of submaximal force (30 Hz), the tetanic myoplasmic free [Ca 2+ ] (measured with the fluorescent indicator indo-1), and fatigue resistance were all impaired by cooling (16-26°C) and improved by heating (36°C). In addition, glycogen resynthesis was faster at 36°C than 26°C in whole flexor digitorum brevis muscles. We conclude that recovery from exhaustive endurance exercise is accelerated by raising and slowed by lowering muscle temperature. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Vaccines for women for preventing neonatal tetanus.

PubMed

Demicheli, Vittorio; Barale, Antonella; Rivetti, Alessandro

2015-07-06

Tetanus is an acute, often fatal, disease caused by an exotoxin produced by Clostridium tetani. It occurs in newborn infants born to mothers who do not have sufficient circulating antibodies to protect the infant passively, by transplacental transfer. Prevention may be possible by the vaccination of pregnant or non-pregnant women, or both, with tetanus toxoid, and the provision of clean delivery services. Tetanus toxoid consists of a formaldehyde-treated toxin that stimulates the production of antitoxin. To assess the effectiveness of tetanus toxoid, administered to women of reproductive age or pregnant women, to prevent cases of, and deaths from, neonatal tetanus. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2015), CENTRAL (The Cochrane Library 2015, Issue 1), PubMed (1966 to 28 January 2015), EMBASE (1974 to 28 January 2015) and reference lists of retrieved studies. Randomised or quasi-randomised trials evaluating the effects of tetanus toxoid in pregnant women or women of reproductive age on numbers of neonatal tetanus cases and deaths. Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Two effectiveness trials (9823 infants) and one safety trial (48 mothers) were included. The main outcomes were measured on infants born to a subset of those randomised women who became pregnant during the course of the studies. For our primary outcomes, there was no high-quality evidence according to GRADE assessments.One study (1182 infants) assessed the effectiveness of tetanus toxoid in comparison with influenza vaccine in preventing neonatal tetanus deaths. A single dose did not provide significant protection against neonatal tetanus deaths, (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.26 to 1.24; 494 infants; GRADE: low-quality evidence). However, a two- or three-dose course did provide protection against neonatal deaths, (RR 0.02, 95% CI 0.00 to 0.30; 688 infants; GRADE: moderate-quality evidence). Administration of a two- or three-dose course resulted in significant protection when all causes of death are considered as an outcome (RR 0.31, 95% CI 0.17 to 0.55; 688 infants; GRADE: moderate-quality evidence). No effect was detected on causes of death other than tetanus. Cases of neonatal tetanus after at least one dose of tetanus toxoid were reduced in the tetanus toxoid group, (RR 0.20, 95% CI 0.10 to 0.40; 1182 infants; GRADE: moderate-quality evidence).Another study, involving 8641 children, assessed the effectiveness of tetanus-diphtheria toxoid in comparison with cholera toxoid in preventing neonatal mortality after one or two doses. Neonatal mortality was reduced in the tetanus-diphtheria toxoid group (RR 0.68, 95% CI 0.56 to 0.82). In preventing deaths at four to 14 days, neonatal mortality was reduced again in the tetanus-diphtheria toxoid group (RR 0.38, 95% CI 0.27 to 0.55). The quality of evidence as assessed using GRADE was found to be low.The third small trial assessed that pain at injection site was reported more frequently among pregnant women who received tetanus diphtheria acellular pertussis than placebo (RR 5.68, 95% CI 1.54 to 20.94; GRADE: moderate-quality evidence). Available evidence supports the implementation of immunisation practices on women of reproductive age or pregnant women in communities with similar, or higher, levels of risk of neonatal tetanus, to the two study sites.

DHS Summer Student Project Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kawamoto, S

2005-08-19

Tetanus and botulinum neurotoxins are among the most potent toxins known to man (Montecucco et al. al., 1995). Produced by the Clostridium tetani and Clostridium botulinum bacteria, respectively, these toxins concentrate in presynaptic axons and inhibit the release of neurotransmitters leading to paralysis and possibly death. Due to the potency of this lethal class of neurotoxins, we have undertaken a project to develop high affinity ligands that specifically bind to these toxins. Such compounds can have significant implications in both the design of detection systems to monitor for the possible release of these neurotoxins into the public and also themore » design of possible therapeutics to treat individuals exposed to tetanus or botulinum neurotoxins. The Clostridial neurotoxins are synthesized as 150 kDa proteins that are post-translationally cleaved into N- and C-terminal fragments held together by a single disulfide bond. The tetanus C-terminal fragment (TetC) has been shown to bind specifically to gangliosides present on the neuronal membrane surface and facilitate endocytosis of the toxin (Morris et al., 1980). Once the toxin is internalized in a membrane-bound vesicle, the light chain (N-terminal fragment) translocates to the cytosol where it interferes with neurotransmitter release. Previous work has demonstrated that various small molecule and peptide-based compounds bind to TetC, albeit in different locations. Among these molecules are the anticancer agent doxorubicin (Dox) and the tripeptides WEY and YEW (Figure 1; Cosman et al. al., 2002). The crystal structure of botulinum toxin and Dox (PDB code: 1I1E) demonstrates that Dox binds in a surface groove of in C-terminal fragment that is conserved in both botulinum and tetanus toxins. Similarly, YEW has been shown to bind to a second binding site that is highly conserved and also relatively close to the binding site of Dox. Thus, in our quest to design and synthesize high affinity ligands, we proposed to link Dox and YEW (or WEY) in hopes of creating a bidentate ligand. In theory, such a ligand could have a binding affinity approaching the product of the two binding affinities of the individual ligands. For my internship project, I was charged with the task of creating libraries of compounds linking Dox and YEW (or WEY) with linkers of varying lengths (Figure 2a). In addition, I was to attach a fluorescein dye to the molecules (Figure 2b) so that they could be used to develop a fluorescence polarization (FP) binding assay. The FP assay will greatly increase the ease with which future ligands can be rapidly screened and binding affinities can be accurately determined. As a side project, I worked on optimizing the conditions necessary to employ the Huisgen 1,3-dipolar cycloaddition reaction to be able to optimize linker lengths and possibly compound solubility (Huisgen, 1984). This reaction, often termed ''click chemistry'', utilizes molecules terminally functionalized with either an acetylene moiety or an azide. In the presence of a copper(I) catalyst, the alkyne and azide undergo a step-wise cycloaddition reaction to link the two molecules together via the formation of a 1,4-disubstituted triazole ring (Figure 3; Rostovtsev et al., 2002). By varying the length of the tethers between the terminal acetylene or azide and their respective molecules, the overall length of the linker between the two molecules can be ''fine tuned'' by one carbon unit at a time. At the completion of my internship I had synthesized conjugates of Doxorubicin and N-acyl-WEY linked together by linkers having 0-2 polyethylene glycol (PEG) linkers. These compounds are currently being used in experiments that employ electrospray ionization mass spectrometry (ESI-MS) to determine whether they bind to TetC with higher affinity than either Dox or WEY alone. I also synthesized the fluorescein tagged versions of the same three molecules. It is expected that these molecules will be used in the near future to develop a fluorescence polarization-based competitive binding assay for TetC and possibly botulinum C-terminal fragment (BotC).« less

Large Solar-Rejection Filter

NASA Technical Reports Server (NTRS)

Roberts, William; Sheikh, David; Patrick, Brian

2007-01-01

NASA utilized Image Intensified Video Cameras for ATV data acquisition from a jet flying at 12.8 km. Afterwards the video was digitized and then analyzed with a modified commercial software package, Image Systems Trackeye. Astrometric results were limited by saturation, plate scale, and imposed linear plate solution based on field reference stars. Time-dependent fragment angular trajectories, velocities, accelerations, and luminosities were derived in each video segment. It was evident that individual fragments behave differently. Photometric accuracy was insufficient to confidently assess correlations between luminosity and fragment spatial behavior (velocity, deceleration). Use of high resolution digital video cameras in future should remedy this shortcoming. A scenically accurate description of matter interpreted as a substance made up of corpuscular constituents was established during the course of the 19th century. In this description, atoms--the building blocks of the matter--form molecules. The properties of the molecules were described by chemistry or thermodynamics depending on what characteristics of the matter were investigated. In both theories, the molecules can dissociate to atoms when the kinetic energies of the atoms exceed the strength of the chemical bonds. The number of atoms is always preserved in a closed system. This is not true, however, when the matter takes up much higher energies at relativistic scales. New particles can be produced at the expense of the kinetic energy. The number of particles is no longer preserved. There are other conserved quantities, however, these quantities, the charge, baryon number, lepton number, are associated with particles that are considered elementary today. The properties and behavior of these elementary particles is the subject of Particle Physics or High Energy Physics. Practice Page: A crewmember touching a positively charged surface was thought to be galvanically isolated from the vehicle ground analogous to a bird on a high voltage power wire. Recent analysis confirms that positive floating potentials, ionospheric currents to the EVA suit, can be hazardous. The analysis is wrong in that the ionospheric plasma itself can close the circuit. Parametric analysis of very low voltage exposures (2 to 15 volts) could cause pain and/or involuntary muscle tetani or spinal cord shock. NASA worked with the Naval Health Research Center Detachment Directed Energy Bioeffects Laboratory to examine the affects electrical hazards could have on extravehicular activity using two models. The results of the two computational models were combined to predict areas of the body in which neurons of different diameters would be excited. They predicted that physiologically active current could be conducted across the crew member causing catastrophic hazards. Future work to analyze additional current paths was proposed. The FUSE spectrum of BB Dor, observed in a high state, is modeled with an accretion disk with a very low inclination (possibly lower than 10 degrees). Assuming an average WD mass of 0.8 solar mass leads to a distance of the order of approximately 650pc, consistent with the extremely low galactic reddening in its direction, and a mass accretion rate of 10 (exp -9) solar mass a year. The spectrum presents some broad and deep silicon and sulfur absorption lines, indicating that these elements are over-abundant: silicon is 3 times solar, and sulfur is 20 times solar. The FUSE spectrum of BB Dor, observed in a high state, is modeled with an accretion disk with a very low inclination (possibly lower than 10 degrees). Assuming an average WD mass of 0.8 solar mass leads to a distance of the order of approximately 650pc, consistent with the extremely low galactic reddening in its direction, and a mass accretion rate of 10 (exp -9) solar mass a year. The spectrum presents some broad and deep silicon and sulfur absorption lines, indicating that these elements are over-abundant: silicon is times solar, and sulfur is 20 times solar. From its previously observed optical emission lines, P831-57 (WD 0334 6400 or Ret 1 in A Catalog and Atlas of Cataclysmic Variables: Living Edition) has been suspected to contain an accretion disk associated with a companion star in orbit around a subdwarf star with a temperature T is greater than 21,000K. P831-57 has therefore been classified as a nova-like. However, our present observations show it to be a DA + dMe binary. The analysis of its Far Ultraviolet Spectroscopic Explorer (FUSE) spectrum (continuum and lines) reveal an average mass white dwarf (Log(g) approximately equals 7.8 plus or minus 0.1)with a temperature T approximately equals 37,000 plus or minus 500K, an extremely low projected rotational velocity, and a distance of about 115 plus or minus 5pc. The photosphere contains C, N, Si, and S (at about 1% of solar abundances). The dMe star is seen as a flux excess in near-infrared photometry and appears to show occasional flaring of about one magnitude as seen in the Harvard plates. There is no evidence of periodic variability in the spectroscopic or photometric data. We find no evidence of a an accretion disk, instead we find evidence of wind accretion as the stellar carbon abundance (N(C)/N(H) = 2.5 x 10 (exp -6) is about ten times larger than predicted by radiative levitation for such a gravity and temperature. The power needs and solutions for the space exploration and lunar mobility program are discussed. Long term missions in space and on the lunar surface require high energy batteries. Rechargeable batteries for mobility systems and portable utility pallet are needed for successful exploration missions. Nanomaterial usage increases the energy density of the cells apart from increasing the power density. The symptoms and threats from acute mountain sickness (AMS) are discussed. The underlying assumptions concerning spacecraft atmosphere mean there is a potential risk to astronauts. The baseline worst case scenario is about 25% based on direct ascent to 8.0 psia with 32% O2. The practical mitigation approach is a staged depressurization scheme. Due to the uncertainty about potential AMS risk the flight surgeon should prepare, focused research should proceed, and current analytical efforts should continue. This slide presentation reviews the threat astronauts face from acute mountain sickness (AMS). The incidence of AMS is highly variable and the risk to astronauts is unclear. However, the potential risk is higher than current EAAs suggest and precautions should be implemented. Due to the uncertain nature of the risk flight surgeons should prepare, and focused research should proceed. Quasiparticle tunneling can be understood at low temperatures using a non-equilibrium kinetic theory. Low-temperature tunneling can be suppressed using existing techniques: island-lead gap engineering, lead cooling with SIN junctions, and quasiparticle traps. The slide presentation reviews the science goals and mission planning for the proposed Jupiter System Observer (JSO). The spacecraft would accommodate 9 instruments making the instrument payload more capable than any previously flown to Jupiter. The would-be mission includes study programs for Jupiter's satellites, interior, magnetosphere and atmosphere. The power needs and solutions for the space exploration and lunar mobility program are discussed. Long term missions in space and on the lunar surface require high energy batteries. Rechargeable batteries for mobility systems and portable utility pallet are needed for successful exploration missions. Nanomaterial usage increases the energy density of the cells apart from increasing the power density. This slide presentation reviews the power requirements for the space exploration and the lunar surface mobility programs. It includes information about the specifications for high energy batteries and the power requirements for lunar rovers,