Age related changes in the skeletal muscle of Calotes versicolor. I. Change in glycogen, total protein, ascorbic acid and water content

Some of the biochemical components of the skeletal muscle of the garden lizard, Calotes versicolor, have been analysedd in relation to age. The glycogen content (mg/100 g wet wt.), reached a peak at about 40 g body weight, followed by a slight decline during the later half of the life span. The total protein (mg/g wet wt.) showed gradual decline till about 40 g bodyweight remaining almost constant thereafter. The total ascorbic acid (mg/100 g wet wt.) declined gradually during the entire life span. A tendency for increase in water percentage with advancing age was observed.     

A serogroup A meningococcal polysaccharide vaccine: studies in the Sudan to combat cerebrospinal meningitis caused by Neisseria meningitidis group A

Vaccination against cerebrospinal meningitis (CSM) has regained interest with the use of capsular polysaccharides (or polyosides) of the meningococcus as specific immunizing agents. These compounds proved to be effective in the USA against meningitis caused by Neisseria meningitidis serotype C. This study considers whether the polysaccharides of the serotype A meningococcus, which is prevalent in the African CSM belt, could be protective in epidemic conditions. Taking advantage of the usual seasonal peak of CSM cases, controlled field trials were undertaken in the Sudan early in 1973. 21 640 persons were vaccinated, half of them with a meningococcal polyoside A vaccine and the other half with tetanus toxoid as a placebo. In the former group there were no cases of meningitis, whereas in the latter 10 cases were reported, of which 7 were confirmed by laboratory tests. These studies indicate that the meningococcal polyoside A vaccine is efficient in epidemic conditions and could be used to control outbreaks of meningococcal meningitis.     

Identification of immunodominant HLA-B7-restricted CD8<Superscript>+</Superscript> cytotoxic T cell epitopes derived from mammaglobin-A expressed on human breast cancers

Mammaglobin-A (MGBA), a 10-kD protein, is over expressed in 80% of primary and metastatic human breast cancers. Breast cancer patients demonstrate high frequencies of CD8⁺ cytotoxic T lymphocytes (CTL) specific to MGBA. Defining CD8⁺ CTL responses to HLA class I-restricted MGBA-derived epitopes assumes significance in the context of our ongoing efforts to clinically translate vaccine strategies targeting MGBA for prevention and/or treatment of human breast cancers. In this study, we define the CD8⁺ CTL response to MGBA-derived candidate epitopes presented in the context of HLA-B7, which has a frequency of 17.7% in Caucasian and 15.5% in African American populations. We identified seven MGBA-derived candidate epitopes with high predicted binding scores for HLA-B7 using a computer algorithm. Membrane stabilization studies with TAP-deficient T2 cells transfected with HLA-B7 indicated that MGBA B7.3 (VSKTEYKEL), B7.6 (KLLMVLMLA), B7.7 (NPQVSKTEY), and B7.1 (YAGSGCPLL) have the highest HLA-B7 binding affinities. Further, two CD8⁺ CTL cell lines generated in vitro against T2.B7 cells individually loaded with MGBA-derived candidate epitopes showed significant cytotoxic activity against MGBA B7.1, B7.3, B7.6, and B7.7. In addition, the same CD8⁺ CTL lines lysed the HLA-B7⁺/MGBA⁺ human breast cancer cell line DU-4475 but had no significant cytotoxicity against HLA-B7⁻ or MGBA⁻ breast cancer cell lines. Cold-target inhibition studies strongly suggest that MGBA B7.3 is an immunodominant epitope. In summary, our results define HLA-B7-restriced, MGBA-derived, CD8⁺ CTL epitopes with all of the necessary features for developing novel vaccine strategies against HLA-B7 expressing breast cancer patients.     

Protective effect of hydrocortisone on iminodipropionitrile-induced neurotoxicity in rats

Occupational and environmental exposure of synthetic nitriles is of potential relevance to human health. Iminodipropionitrile (IDPN), a prototype nitrile toxin, has been shown to produce dyskinetic syndrome in rodents. This study reports the effect of concomitant exposure of rats to hydrocortisone and IDPN on behavioural abnormalities namely excitation, circling and chorea (ECC) syndrome. Four groups of female Wistar rats were given hydrocortisone (0, 10, 30 and 60 mg/kg, gavage, for 10 days) 30 min. before IDPN (100 mg/kg, intraperitoneally for 8 days). Two additional groups of rats were treated with either saline (control group) or 60 mg/kg of hydrocortisone (drug alone group). The animals were observed for neurobehavioural abnormalities including dyskinetic head movement, circling, tail hanging, air righting reflex and contact inhibition of righting reflex. After behavioural studies, the animals were killed, and the discrete brain regions and temporal bones were collected for biochemistry and inner ear histopathology, respectively. Hydrocortisone significantly and dose dependently attenuated the incidence and severity of IDPN-induced behavioural syndrome. Administration of hydrocortisone (60 mg/kg) alone significantly increased glutathione (GSH) levels in olfactory bulb and striatum, whereas IDPN alone significantly reduced GSH levels in olfactory bulb, striatum and hippocampus. Hydrocortisone (60 mg/kg) significantly compensated IDPN-induced depletions of GSH in different brain regions. Hydrocortisone also protected the animals against IDPN-induced vestibular hair cell degeneration. The protective effect of hydrocortisone may be attributed to its anti-inflammatory and antioxidant properties.     

Time-course evaluation of whole blood phagocytosis in mice treated with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Immunological abnormalities have been described in idiopathic Parkinson's disease and in the mouse model of this disorder induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This investigation was aimed to study the effect of MPTP on inflammatory response of whole blood phagocytes at different time intervals. C57BL male mice were injected intraperitoneally with either MPTP (30 mg/kg) or saline (control group) and the blood samples were collected at 4, 24 and 48 h. 50 l of a 500-fold diluted blood sample was mixed with 150 l of reaction mixture (0.4 mM luminol + 50 g opsonized zymosan + 0.1% gelatin, in Hanks' balanced salt solution) and the chemiluminescence (CL) signal was measured in a luminometer at 37°C. Although the CL response of the whole blood from control and MPTP groups was similar at 4 h, a significant increase in the CL signal was observed in MPTP-treated mice at 24 h post-treatment, which got subsided at 48 h. The findings of this study suggest that in an early stage a pro-inflammatory response following MPTP might trigger a chain of potentially toxic pathways mediated by reactive oxygen species, leading to progressive neuronal damage.     

Protective effects of nedocromil sodium and sodium cromoglycate on gastroduodenal ulcers: a comparative study in rats

Stabilization of mast cells plays a key mechanism to protect gastrointestinal tract from injury. This study presents a comparative evaluation of mast cell stabilizers nedocromil sodium (NDS) and sodium cromoglycate (SCG) in experimental gastric and duodenal ulcers in rats. Wistar rats of either sex were used in this study. Both NDS and SCG, in the doses of 10, 30 and 100 mg/kg were given intraperitoneally for gastric secretion studies and by gavage for antiulcer studies. Acid secretion studies were undertaken in pylorus-ligated rats. Gastric lesions were induced by water immersion restraint stress (WIRS), indomethacin and ethanol whereas duodenal ulcers were produced by cysteamine. The level of glutathione (GSH) and gastric wall mucus were measured in glandular stomach of rats following ethanol-induced gastric lesions. SCG was more effective than NDS in preventing WIRS- and indomethacin-induced gastric lesions whereas reverse was true in ethanol- and cysteamine-induced ulcers. All the 3 doses of SCG offered almost equal protection against WIRS-induced gastric lesions whereas only medium and high dose of NDS provided significant protection in this model of ulcer. NDS significantly inhibited cysteamine-induced duodenal ulcers whereas SCG failed to do so. Pretreatment with NDS or SCG significantly and dose-dependently protected gastric mucosa against ethanol-induced injury, while the former drug appeared to be more effective. The cytoprotective effects of these two drugs were accompanied by the attenuation of ethanol-induced depletion of gastric wall mucus and GSH. The differential effects of NDS and SCG against various gastric lesions rationalize the possible benefits of a combined therapy (NDS+SCG) for the treatment of complex gastroduodenal ulcers. Received 29 April 2006; revised: 26 May 2006; accepted: 26 May 2006     

Age related changes in the skeletal muscle of Calotes versicolor. II. Correlation between RNA, total protein and free amino acids pool; changes in protein fractions

The RNA content of the skeletal muscle of the garden lizard, Calotes versicolor declined sharply till maturity, remaining constant thereafter. Correlated with this, the total protein content showed a decreasing age related trend and the free amino acids pool a rising tendency. The “myogen” protein fraction of the skeletal muscle showed increasing accumulation till maturity, followed by a slower decline. The concentration of contractile protein fraction (myosin and actin) increased with advancing age and that of stroma protein declined sharply till maturity remaining almost constant thereafter.     

Longevity of Middle East Respiratory Syndrome Coronavirus Antibody Responses in Humans,Saudi Arabia

Understanding the immune response to Middle East respiratory syndrome coronavirus (MERS-CoV) is crucial for disease prevention and vaccine development. We studied the antibody responses in 48 human MERS-CoV infection survivors who had variable disease severity in Saudi Arabia. MERS-CoV–specific neutralizing antibodies were detected for 6 years postinfection.