Determinants of dysphagia following stroke

Background:Swallowing is affected following stroke. Many studies focus on various aspects of swallowing difficulties (dysphagia) following stroke. However, there are not many studies on the determinants of dysphagia following stroke. The aim of the present study is to establish the association between various factors with the severity of dysphagia. Methods: After screening for Mann Assessment of Swallowing Ability (MASA),110 patients, post-stroke were selected using consecutive sampling to assess the common risk factors, namely the presence of diabetes mellitus, dyslipidemia, hypertension, alcohol usage and smoking habits. Additionally, other variables such as age, gender, type of lesion, side of lesion, tobacco chewing, speech disorders, arterial dysfunction, lobe involvement and Brunnstrom's stages, were also evaluated using a structured interview method. 2 (chi-squared) analysis was carried outto find out the association between the selected determinants and severity of dysphagia following stroke.Results: It was found that age and Brunnstrom's stages are the determinants of dysphagia, as analysis showed a strong association with a p value < 0.001. A marginal association between post-stroke dysphagia and type of lesion with a p value of 0.056 was also observed.Conclusions: Among15 factors evaluated, age, type of lesion and Brunnstrom's stages showed a significant association with the severity of dysphagia following stroke. This study advocates early dysphagia management for elderly patients with high Brunnstrom's grading, for those who are not expected to spontaneously recover following stroke, and for earlier and better community rehabilitation

Short term inhalation exposure to silica aerosol on respiratory parameters monitored by online computer programme in mice

Silicosis or pulmonary fibrosis is caused by inhaling dusty air polluted with silica. It is an occupational hazard for workers in construction industry as well as mining. While there are studies available on long term exposure to such dust, reports on short term exposure are scarce. Hence, in the present study, we exposed mice to silica aerosol repeatedly and monitored the respiratory parameters during inhalation by online computer programme for short term. Mice were exposed in a head-out-body-plethysmograph to 150 mg m-3 of silica aerosol generated by an airblast nebulizer for 4 h and for 5 days continuously. The respiratory changes were monitored by a volumetric pressure transducer and analyzed by an online computer programme capable of quantifying the breathing pattern and the respiratory variables. Immediately after the start of silica inhalation the normal breathing pattern decreased and airway obstruction pattern increased. There was no sensory or pulmonary irritation pattern. Correspondingly, the frequency increased and the tidal volume decreased. After the end of inhalation exposure, only partial recovery was observed. On the next day, the respiratory frequency was increased and the tidal volume decreased before the start of silica inhalation compared to the previous day. Following exposure to silica on subsequent days the respiratory frequency further increased and the tidal volume decreased. This study shows that silica aerosol inhalation can cause an immediate change in the respiratory variables with an increase in the respiratory frequency and decrease in tidal volume (rapid shallow breathing), and a breathing pattern of airway obstruction.

A comparative study of the effect of amikacin administered through autoinjector and manual injection on biochemical parameters in rats.

Objective: The objective was to compare the biochemical changes of amikacin by autoinjector delivery and manual injection in rats. Materials and Methods: Amikacin drug cartridge (500 mg/2 mL) for autoinjectors was diluted to 63 mg/mL and rats were administered 1.2 mL, i.p. One group was given 3 and a second group 7 injection on consecutive days. 3 and 7 days manual injection of same dose of amikacin (about 500 mg/kg, i.p.) and a control group (saline) were also included (total 5 groups). On day 4 or 8 biochemical parameters were studied. Results: Significant increase in urea, creatinine and aspartate aminotransferase were observed in 7 days administration in both autoinjector and manual injection groups compared to control group. All other parameters viz., glucose, cholesterol, total triglycerides, bilirubin, uric acid, total protein, albumin, alanine aminotransferase and alkaline phosphatase did not show any significant change. No significant change was observed in 3 days administration groups. Conclusion: High dose of amikacin for longer duration is known for its nephrotoxicity which is evidenced by the increase in urea and creatinine in both autoinjector and manual injection groups. This study shows that autoinjector device for amikacin which is new can be considered for further research work.

Purification of Catalase Enzyme from Pleurotus Ostreatus.

The oyster mushroom Pleurotus ostreatus is the most commonly cultivated mushroom, and are effective for antitumor, antibacterial, anti viral and hematological agents and in immune modulating treatments. Several compounds from oyster mushrooms, potentially beneficial for human health have been isolated and studied. The aim of this research is to purify an enzyme catalase from Pleurotus ostreatus through Sephadox G-75 column, its molecular weight was determined by polyacrylamide gel electrophoresis and the catalase enzyme stability were observed at various temperature and different pH condition. Under denaturing conditions, polyacrylamide gel electrophoresis revealed dissociation of a major component of molecular weight 62,000 kDa, which constituted 90% of the total protein of the stained gel, suggesting that the native enzyme is tetrameric. The optimum temperature and pH for the purified enzyme catalase from Pleurotus ostreatus enzymatic reaction were 30°C and pH 7.5.

A convenient first aid kit for chemical and biological agents and for radiation exposure.

The chemical and biological warfare agents are extremely toxic in nature. They act rapidly even in very small quantities and death may occur in minutes. Hence, physical and medical protection must be provided immediately to save life or avoid serious injury. A first aid kit has thus been developed for providing immediate relief from chemical and biological warfare agents (FAKCBW) with the objective of easy detection, personal decontamination, antidote for chemical warfare agents (like nerve agents, sulphur mustard, phosgene, cyanide, radiation exposure and bacterial agents), along with basic medication aid for pain, fever and inflammation. The kit box also includes a user friendly handbook with a simple standard operating procedure. In addition, the kit is rugged to withstand normal jerks, vibration and is water-proof.

Nitrogen and sulphur mustard induced histopathological observations in mouse visceral organs.

Nitrogen mustards (HN) and sulphur mustard (SM) are potent alkylating blister inducing chemical warfare agents. Single 1.0 LD50 dose produced a progressive fall in body weight from second day onwards in all groups of mustard agents exposed animals. Histological examination of spleen, liver, skin and kidney revealed significant histopathological lesions in nitrogen mustards and sulphur mustard. These lesions include granulovascular degeneration with perinuclear clumping of the cytoplasm of hepatocytes and renal parenchymal cells. Renal lesions were characterized by congestion and hemorrhage. The maximum toxic manifestation were noted in spleen and skin of HN-3 exposed mice while sulphur mustard reported maximum toxicity in liver and kidneys. The study suggests both nitrogen mustards and sulphur mustard to be extremely toxic by percutaneous route based on histopathological observation and can contributed to earlier reported free radical generation by these toxicants.

Impact of phase zero trials (micro-dosing) in clinical trial research.

ABSTRACT : Currently, pre-clinical trials using animal models, cell culture methods and bio-informatics takes up to 18 months and the typical development for investigational new drugs takes between ten to fifteen years and associated with high cost and low rate of approval. Phase 0 trials are attractive approach and in future would require only few preclinical studies, phase I trial and a reduced amount of the investigational new experimental drug on human. FDA supports the conduct of phase 0 trials in oncology related studies. The negative points pertaining to phase 0 trials is that the drug and dose is too small and reliable biomarkers are too thin on the ground despite great sum of money being spent to find and validate them. Phase 0 clinical trials can decrease the cost and time and could improve the process of drug development in future. In this review, we try to provide the recent developments and impact of phase zero trials in clinical trial research. Abbreviations FDA (Food and Drug Administration:USA), NOAEL (No Observed Adverse Effect Level)ADME(Absorption,Distribution,MetabolismandExcretion)

Prophylactic efficacy of combination of DRDE-07 and its analogues with amifostine against sulphur mustard induced systemic toxicity.

Sulphur mustard, [bis (2-chloroethyl)] sulphide (SM), is a bifunctional alkylating agent. SM forms sulphonium ion in the body which alkylates DNA and several other macromolecules, and induces oxidative stress. Although several antidotes have been screened for the treatment of systemic toxicity of SM in experimental animals none of them are recommended so far. In the search for more effective and less toxic antidotes, various combinations were tried against SM induced toxicity and skin lesions. SM exposed through percutaneous route was used to evaluate the prophylactic efficacy of various combinations. Low dose of DRDE-07 (S-2(2-aminoethylamino) ethyl phenyl sulphide), DRDE-30 [S-2(2-aminoethyl amino) ethyl propyl sulphide], DRDE-35 [S-2(2-aminoethyl amino) ethyl butyl sulphide] with amifostine combinations, were given orally 30 min prior to SM exposure. Significant depletion was observed in body weight, organ body weight index and hepatic GSH and GSSG content in mice after SM exposure. Pretreatment with low dose of different combinations of DRDE-07, DRDE-30 and DRDE-35 with amifostine could recover biochemical alterations and histopathological changes caused by SM exposures.

Acute and sub-acute toxicity of an insect pheromone, N-heneicosane and combination with insect growth regulator, diflubenzuron, for establishing no observed adverse effect level (NOAEL).

Aedes aegypti mosquito is one of the most notorious vectors of dangerous diseases like dengue hemorrhagic fever and chikangunya. One method of control of the vectors is by the use of semiochemicals or pheromones. The pheromone n-heneicosane (C21) has been proved to be effective in attracting the female Aedes aegypti to lay eggs in the treated water and the growth of the larva is controlled by insect growth regulator diflubenzuron (DB). This study was planned to assess the safety of C21 alone and the combination with DB. Acute toxicity tests were carried out using two doses, viz., 1600 and 3200 mg/kg and two routes of exposure oral and intra-peritoneal. Dermal toxicity test was carried out in both male and female rats at the dose of 3200 mg/kg. Primary skin irritation test was carried out in rabbits. Sub-acute (90 days) dermal toxicity studies in male and female rats at the dose of 1 and 2 mg/kg via the per-cutaneous route were also studied. Sub-acute (90 days) toxicity test through the oral route was carried out, at doses 125, 250 and 500 mg/kg in male and female rats. The calculated LD50 by ip route and dermal route was more than 5 g/kg in mouse and rats of both the sexes. In the primary skin irritation test no significant changes were noted. In the sub-acute toxicity studies even 500 mg/kg dose was not able to produce toxic response in rats when they were dosed daily for 90 days. The established no observed adverse effect level (NOAEL) was more than 500 mg/kg.

Comparison of toxicity of selected mustard agents by percutaneous and subcutaneous routes.

Comparative toxicity of nitrogen mustards (HN-1, HN-2 and HN-3) and sulphur mustard was carried out in mice. Based on LD50, the toxicity pattern was HN-2 < HN-1 < HN-3 < sulphur mustard by percutaneous route whereas, by subcutaneous route the toxicity pattern was sulphur mustard < HN-3 < HN-2 < HN-1. Single dose of 1 LD50 of nitrogen mustards and sulphur mustard was administered percutaneously and various oxidative stress parameters were also evaluated. The weight loss was more in HN-2 on day 3 and in sulphur mustard on day 7. There was a drastic fall of WBC count on day 3 in all groups with a recovery in nitrogen mustard groups on day 7. The RBC count and haemoglobin content showed a significant increase on day 7 in sulphur mustard group. The plasma enzymes (ALT, AST and ALP) showed an increase in all groups on day 3 and day 7. The hepatic GSH and GSSG contents were reduced and MDA content increased in all groups, with a further change in sulphur mustard on 7 day. Extensive DNA fragmentation was observed in all the nitrogen mustard groups compared to sulphur mustard group, on day 3. However, on the day 7 the DNA fragmentation was same in all groups. This study showed that the nitrogen mustards and sulphur mustard were extremely toxic by percutaneous route and caused oxidative stress. Sulphur mustard was more toxic by the percutaneous route and the effects were delayed and progressive.

Protective effect of ethanolic and water extracts of sea buckthorn (Hippophae rhamnoides L.) against the toxic effects of mustard gas.

Ethanolic extract of H. rhamnoides L. leaf (HL-EOH), water and ethanolic extract of H. rhamnoides fruit (HF-W and HF-EOH), and H. rhamnoides flavone from fruit (HR-flavone) were evaluated against percutaneously administered sulphur mustard (SM), a chemical warfare agent. The animals administered with SM (9.7, 19.3 and 38.7 mg/kg) died at various days depending upon the dose and there was a significant reduction in the body weight. The H. rhamnoides extracts (1 g/kg; 3 doses; po) significantly protected the lethality, with a protective index of 2.4, 1.7, 1.7 and 2.2 for HL-EOH, HF-W, HF-EOH and HR-flavone respectively. Reduced glutathione (GSH) and oxidized glutalthione (GSSG) levels were reduced, and malondialdehyde (MDA) was elevated after percutaneous administration of SM. Oral administration of HL-EOH and HR-flavone significantly protected the body weight loss. Recovery in the levels of GSH, GSSG and MDA were also observed following oral administration of HL-EOH and HR-flavone. All the extracts were non-toxic and the LD50 was more than 5 g/kg. The present study shows that percutaneous administration of SM induces oxidative stress and ethanolic extract of leaf of H. rhamnoides and H. rhamnoides flavone from fruit can significantly protect it.

Inflammatory fibroid polyp of jejunum causing jejuno-jejunal intussusception.

Intussusceptions originating in the jejunum are rare. We report a 20-year-old woman who had a chronic jejuno-jejunal intussusception due to an inflammatory fibroid polyp manifesting in the post-partum period as peritonitis. Resection-anastomosis of the intussuscepted segment was done. She is well one year later.

True giant intra-abdominal esophageal cyst.

Isolated intra-abdominal duplication cysts of foregut origin are extremely rare and are discovered incidentally. We report a 70-year-old lady with a giant, truly intra-abdominal esophageal duplication cyst. She was symptom-free one year after excision of the cyst.

Dose response of sulphur mustard: behavioral and toxic signs in rats.

The present study elucidates the behavioral and toxic signs in rats following dermal application of sulphur mustard (SM). Graded doses of SM (0.10, 0.25, 0.50, 0.75 and 1.0 LD50) were topically applied to male Wister rats. The body weight as well as behavioral/toxic signs and symptoms were recorded at 1, 2, 3, and 4th day after application of SM. Sulphur mustard consistently decreased body weights of rats in a dose and time dependent manner with maximum decrease on 3rd day post treatment. Sedation and diarrhea were significant in response to doses of SM intoxication in rats. It is concluded that the body weight, sedation and diarrhea may be used as a reliable parameter in evaluating SM intoxication. It is also suggested that hydration and hypertonic saline must be used as a rescue agent within 1-3 days after exposure to SM.

Influence of pretreatment of carbamates on dynamic pulmonary mechanics in rats exposed to sarin aerosols.

The effect of pretreatment of two carbamates, pyridostigmine and physostigmine on dynamic pulmonary mechanics has been studied in rats exposed to sarin aerosols. Sign-free dose of pyridostigmine (0.075 mg/kg, i.m.) or physostigmine (0.1 mg/kg, i.m.) did not significantly alter the parameters of the dynamic pulmonary mechanics 20 min after treatment. However, sarin (51.2 mg/m3, for 15 min) depressed the respiratory rate, air flow and minute volume and enhanced the transthoracic pressure and tidal volume. Pretreatment with carbamates 20 min prior to sarin exposure significantly modified or counteracted the above induced changes. It is concluded that the protective effect of carbamates is mainly due to the correction of respiratory changes caused by sarin aerosols in rats.

Biochemical and pathological changes in response to hyperoxia and protection by antioxidants in rats.

A significant decrease in blood haemoglobin, reduced glutathione and protein in lung and liver, without any change in blood reduced glutathione, was observed in rats exposed to 80% oxygen. Hydrogen peroxide induced erythrocyte haemolysis was significantly increased following exposure to hyperoxia. The lungs of rats exposed to hyperoxia showed perivascular edema. Simultaneous treatment with antioxidants, vitamin A, C, or E, protected the animals against oxygen toxicity.

DFP induced changes in acetylcholinesterase activity and glycogen level in certain brain regions of mice.

DFP in acute dose (2 mg/kg i. p.) in mice significantly inhibited acetylcholinesterase AChE) activity in five regions of brain i.e. cerebral cortex, corpus striatum, medulla, cerebellum and hypothalamus. The inhibition was accompanied by depletion of glycogen from these regions 1 hr after DFP administration. The inhibition of enzyme activity was more in corpus striatum and medulla and glycogen depletion was more in cerebral cortex in comparison to other regions of the brain. These changes may be due to stimulatory effect of DFP on these regions of brain in mice.

Effect of subacute exposure to methyl isocyanate on testicular histomorphology in mice.

Mice exposed to methyl isocyanate (MIC; 134 mg.m-3 for 30 min = 4020 mg.min-1.m-3) showed a marked loss of body weight after 24 hr and the mean body weight of the exposed group was significantly less than the control, even 15 days after the exposure. No significant change was observed on relative testicular weight. Spermatozoa in the seminiferous tubules disappeared 3 days post exposure. Primary and secondary spermatocytes were hypertrophied. Normalization occurred after 15 days.