Evaluation of nanoformulated therapeutics in an ex-vivo bovine corneal irritation model.

AIM: To determine the internalization and protective effects of potential ophthalmic formulations and nanoformulated natural proteins in ex-vivo bovine corneal alkali burn model. METHODS: The bovine cornea obtained were subjected to the 0.5N NaOH insult that induced alkali burn and inflammation as observed in the in vivo situation. The toxic effects of the nanoformulation were evaluated in the normal and insult induced cornea using histological analysis. Internalization studies were carried out using in vivo imaging and analysis (IVIS, PerkinElmer, USA). RESULTS: The nanoformulations employed in this study showed no obvious changes in the integrity of the cornea. Further, improvements in the light transmittance and reduced inflammation were observed. The IVIS showed a dose dependant increase in the uptake of the nanoformulations with time. CONCLUSION: The nanoformulated bovine lactoferrin and SurR9-C84A (SR9) proteins evaluated in the ex vivo bovine corneal irritation model is the first of its kind, and we report here the non-toxic and therapeutic potential of these formulations for topical applications.

Cyclic Vomiting Syndrome: A Functional Disorder.

Cyclic vomiting syndrome (CVS) is a functional disorder characterized by stereotypical episodes of intense vomiting separated by weeks to months. Although it can occur at any age, the most common age at presentation is 3-7 years. There is no gender predominance. The precise pathophysiology of CVS is not known but a strong association with migraine headaches, in the patient as well as the mother indicates that it may represent a mitochondriopathy. Studies have also suggested the role of an underlying autonomic neuropathy involving the sympathetic nervous system in its pathogenesis. CVS has known triggers in many individuals and avoiding these triggers can help prevent the onset of the episodes. It typically presents in four phases: a prodrome, vomiting phase, recovery phase and an asymptomatic phase until the next episode. Complications such as dehydration and hematemesis from Mallory Wise tear of the esophageal mucosa may occur in more severe cases. Blood and urine tests and abdominal imaging may be indicated depending upon the severity of symptoms. Brain magnetic resonance imaging and upper gastrointestinal endoscopy may also be indicated in certain circumstances. Management of an episode after it has started ('abortive treatment') includes keeping the patient in a dark and quiet room, intravenous hydration, ondansetron, sumatriptan, clonidine, and benzodiazepines. Prophylactic treatment includes cyproheptadine, propranolol and amitriptyline. No mortality has been reported as a direct result of CVS and many children outgrow it over time. A subset may develop other functional disorders like irritable bowel syndrome and migraine headaches.

Cyclic Vomiting Syndrome: A Functional Disorder / 대한소아소화기영양학회지

Cyclic vomiting syndrome (CVS) is a functional disorder characterized by stereotypical episodes of intense vomiting separated by weeks to months. Although it can occur at any age, the most common age at presentation is 3-7 years. There is no gender predominance. The precise pathophysiology of CVS is not known but a strong association with migraine headaches, in the patient as well as the mother indicates that it may represent a mitochondriopathy. Studies have also suggested the role of an underlying autonomic neuropathy involving the sympathetic nervous system in its pathogenesis. CVS has known triggers in many individuals and avoiding these triggers can help prevent the onset of the episodes. It typically presents in four phases: a prodrome, vomiting phase, recovery phase and an asymptomatic phase until the next episode. Complications such as dehydration and hematemesis from Mallory Wise tear of the esophageal mucosa may occur in more severe cases. Blood and urine tests and abdominal imaging may be indicated depending upon the severity of symptoms. Brain magnetic resonance imaging and upper gastrointestinal endoscopy may also be indicated in certain circumstances. Management of an episode after it has started ('abortive treatment') includes keeping the patient in a dark and quiet room, intravenous hydration, ondansetron, sumatriptan, clonidine, and benzodiazepines. Prophylactic treatment includes cyproheptadine, propranolol and amitriptyline. No mortality has been reported as a direct result of CVS and many children outgrow it over time. A subset may develop other functional disorders like irritable bowel syndrome and migraine headaches.

Jervell and Lange-Nielsen syndrome in a father and daughter from a large highly inbred family: a 16-year follow-up of 59 living members.

OBJECTIVE: To report the autosomal dominant inheritance of the Jervell and Lange-Nielsen syndrome in a highly inbred family, the initiation of Torsades de Pointes, and the natural history of the syndrome based on a 16-year follow-up of the kindred. METHOD: A family tree was constructed that included 66 blood relatives from three successive generations. Electrocardiograms were obtained from 59 living members including the proband, four members from a nuclear family, and 54 from the extended family. Evoked response audiometry was recorded for the proband and the nuclear family. All 59 family members were followed up regularly for 16 years. RESULTS: A total of 24 living members were affected--QTc: 480-680 ms. The proband had long QTc, bilateral high-tone sensorineural deafness, recurrent syncope, and Torsades de Pointes. The asymptomatic father had long QTc and unilateral high-tone sensorineural deafness that involved specifically the left ear. One asymptomatic sibling of the proband had long QTc and normal hearing. The mother and another sibling were asymptomatic; QTc and hearing were normal in both. A total of 21 affected members from the extended family had only long QTc, and all were asymptomatic. There were three congenitally deaf first cousins who had recurrent syncope and adrenergic-triggered sudden death. In all, seven of 10 parents had consanguineous marriage to a first cousin. Each affected offspring had at least one affected parent. The severely symptomatic proband who received only ß-blocker therapy and the 23 affected members without antiadrenergic therapy, all remained asymptomatic throughout the 16-year follow-up period. CONCLUSION: Jervell and Lange-Nielsen syndrome was inherited as autosomal dominant in this kindred. The majority of the affected members had a mild phenotype. The severity of auditory and cardiac phenotypes corresponded.

Human spermatozoal motility and lipid peroxidation.

Correlation between human spermatozoal motility and lipid peroxidation is worked out following their suspension in native seminal plasma and in Biggers, Whitten and Whittengham (BWW) medium. Spermatozoa suspended in BWW showed higher motility and lesser degree of lipid peroxidation than those suspended in seminal plasma. Further, higher activities of antioxidant enzymes are recorded in the BWW suspended spermatozoa vis a vis those suspended in native seminal plasma.

Effect of vitamin E on human sperm motility and lipid peroxidation in vitro.

AIM: To assess the protective efficacy of vitamin E to counteract the reactive oxygen species (ROS) mediated damage on sperm motility, viability and lipid peroxidation. METHODS: Human semen samples were obtained from the local hospital. The split seminal fractions freed of seminal plasma were reconstituted in Ringer-Tyrode and subjected to varied vitamin E concentrations (0.1-2 mmol/L). RESULTS: Dose-dependent improvement in both motility and viability accompanied by concomitant decrease in malondialdehyde (MDA--an end product of lipid peroxidation) following vitamin E supplementation was noticed. CONCLUSION: Vitamin E protects against the ROS mediated damage on spermatozoa. Vitamin E supplementation could be of clinical importance for prolonged spermatozoal storage whenever needed.

Human sperm motility and lipid peroxidation in different ascorbic acid concentrations: an in vitro analysis.

Human spermatozoal motility, viability and lipid peroxidation (LPO) have been assessed in Ringer-Tyrode supplemented with different concentrations of ascorbic acid (AA) ranging from 50 to 4000 microM. Ascorbic acid in concentrations below 1000 microM protects spermatozoa from free radical damage as evidenced from improvement in their motility and viability. Concomitantly, there is also witnessed depletion of malondialdehyde generation (an end product of LPO) following AA treatment. Ascorbic acid at 1000 microM concentration and above, however, is not protective, as evidenced by abrupt fall in sperm motility and viability and concomitant increase in LPO.

Evaluation of Internet-based oncologic teaching for medical students.

BACKGROUND: Electronic tools with substantial educational applications are now widely available. METHODS: In a prospective, randomized study, the value of Web-based educational tools for teaching second-year medical students was evaluated. The 35-hour, image-intensive multifaculty neoplasia course was selected for the experiment, with 103 students assigned to the control group (C) and 61 to the experimental group (E). Representative password-controlled multimedia course modules, accessible via the Internet, were developed. The E cohort was exposed to both classroom and Web-aided materials, whereas the C group had access to the Web modules only after the experiment was concluded (but before the final examination). Pre- and post-exposure questionnaires assessed computer knowledge, familiarity with the Internet, availability of computer access, and the value of Web-based education for both cohorts. Additionally, pre-and post-exposure tests were administered to both cohorts based on educational materials presented in the Web modules. RESULTS: The overall participation rate was 64% (E = 69%; C = 60%). The post-test showed no major performance difference between the two groups. The questionnaires revealed that: less than 1% of the students had not accessed the Internet previously; less than 5% had not used the Internet for medical education before; 34% felt that computer resources on campus were inadequate; and over 75% found Web-based education to be an important additional educational resource. The major negative aspect was the slow pace of data transfer for modem-based home access. Only 1% of students felt that Web-based education could completely replace traditional teaching. CONCLUSION: The potential for incorporating Web-based education in the medical curriculum is considerable.

Alterations in the hematological profile in rat following whole body gamma radiation with and without venoruton pretreatment.

The radioprotective effect of venoruton [O-(beta-hydroxyethyl)-rutoside] has been assessed in the hematological profile of Swiss albino male rats subjected to a single dose of 300 rads whole body gamma radiation. The results showed that the severity of the radiation-induced abnormalities in the red and white blood cells is significantly lessened by venoruton administered prior to radiation exposure.

Hematological lesions in rat following heavy alcohol ingestion.

Hematological fluctuations following large alcohol oral administration (2 mL per animal per day) in rats were monitored at intervals ranging from 10 to 22 weeks and the findings were compared to those in control animals that were fed sucrose isocalorically. Following alcohol ingestion, there was a significant decrease in the total blood cellularity at all treatment intervals. A fall in the erythrocyte count per millimeter3 was accompanied by decreased hematocrit values and hemoglobin levels in the alcohol-treated animals. On the other hand, the MCV and MCH values were significantly elevated after alcohol ingestion. Despite overall leukopenia observed after alcohol ingestion, there was a significant increase in the absolute neutrophil count. The absolute lymphocyte count, however, fell significantly in the alcohol-treated animals. Eosinophils and basophils were not significantly altered by alcohol toxicity.

Venoruton as a radioprotector: a haematological assessment.

Efficacy of Venoruton--O-(hydroxyethyl) Rutoside--as a radioprotector has been tested on haematological profile of rats which were subjected to whole body radiation (500 rads). The results show radiation induced lesions in respect of total (TLC) and differential leukocyte counts (DLC)/and haemoglobin are significantly lessened when Venoruton was administered prior to radiation exposure.

Phospholipid composition of Mycobacterium smegmatis susceptible and resistant to antitubercular drugs.

The phospholipid composition, distribution and metabolism in mono drug resistant mutants towards antitubercular drugs, viz, streptomycin, ethambutol and isoniazid, were investigated. Though their total phospholipid content was not altered significantly, changes were observed in their individual phospholipid content. Reduced biosynthesis and degradation of phospholipids (monitored by pulse and chase technique using [32P]orthophosphoric acid as a precursor) was observed in all the mutants studied. The subcellular distribution of phospholipids revealed accumulation of phospholipids in the cell walls and reduction in cell membranes of the drug-resistant mutants. Similar alterations were seen in individual phospholipids of these subcellular fractions.

Characterization of specific insulin binding sites in rat testis following induced diabetes and experimental starvation.

The presence of insulin-saturable binding sites in the rat testis have been demonstrated. Employing radioreceptor assay (RRA), the characteristics of insulin binding in both liver and testis of the normal (control) rats have been studied. Crude receptor binding at 37 degrees C after 18-20 hrs of incubation in Tris-HCl buffer at pH-7.5. The binding of 125I-insulin to liver and testis of the experimental rats, rendered diabetic for two months with single parenteral streptozotocin (STZ) administration (65 mg/Kg, BW, ip) was also studied. In the diabetic rats, the insulin binding in liver as compared to the control increased by over 92% (P 0.001); the increase in the binding of 125I-insulin to the testis of the diabetic rats however was not statistically significant. Similarly, insulin binding to the testis did not vary much after 3 days of starvation as against 84% (P 0.001) increase in the insulin binding to the liver of the fasted rats. These results suggest that testicular insulin receptors are similar to those of liver but may have a different physiological control.

Heavy lithium ingestion and haematological changes in rats.

Haematological lesions (viz. total leukocyte count, differential leukocyte count, RBC count, haematocrit value) have been studied in both adults and freshly weaned rat pups following heavy oral (50 mg/kg b.wt.) lithium administration for 2 months. Significant increase in the total leukocyte count/mm3 and neutrophil count/mm3 accompanied by concomitant fall in the lymphocyte count/mm3 was observed in both the adults and weaned rat pups at all the treatment intervals. Erythrocyte count and the haematocrit values were also significantly increased in both the treated adults and pups as compared to their age matched controls. Physiological significance of these haematological fluctuations has been discussed.

Enzyme changes in the brain, liver and kidney following repeated administration of mercuric chloride.

Alterations in the levels of selected enzymes have been studied in the liver, kidney and brain of mouse following mercuric chloride (1 mg/Kg body wt./d) administration for 10, 20 and 30 d. The activity of acid phosphatase increased in all the tissues, the highest increase was recorded in the kidneys which showed as much as 4.5 fold elevation following mercuric chloride administration for 30 d. Although the alkaline phosphatase activity in the liver and the brain increased following HgCl2 administration, the kidneys experienced a tremendous decline in this enzyme following the same treatment. Mercury-induced changes in ATPase were complex inasmuch as the nature and magnitude of these changes varied with the tissue as well as the duration of the treatment. Whereas the liver ATPase declined after all the treatment intervals, this enzyme increased in the kidney and brain following administration of HgCl2 for 10 d. However, both the kidneys and brain registered a substantial fall in ATPase activity when HgCl2 administration was continued for 30 d. The levels of both glucose-6-phosphatase and succinic dehydrogenase decreased in all the tissues following HgCl2 administration. Invariably, the magnitude of decrease was the highest after 30 d treatment with HgCl2.

Clearance of parenterally administered 203Hg from the mouse tissues.

Peak 203Hg levels in the liver, kidney, spleen, lungs and the heart of mouse following a single intraperitoneal administration, fell exponentially. Half-clearance time of 203Hg is the longest in the kidney (50 hr) followed by the liver (38 hr), spleen (25 hr) and the heart and lungs (16 hr).