Induction of ultraviolet cataracts in vitro: prevention by pyruvate.

Ultraviolet (UV) radiation is one of the important cataract risk factors. The present studies examined the hypothesis that this effect is due to the UV penetration through the cornea and subsequent induction of a photochemical generation of reactive species of oxygen (ROS) in the aqueous and lens. The hypothesis was ascertained by rat lens organ culture studies conducted under UV (365 nm), with media containing micromolar levels of riboflavin, with and without pyruvate, the latter acting as an ROS scavenger. The implication of ROS in the UV-induced damage was confirmed by measurements of peroxide generation. Damage to the lens was assessed physiologically by measuring the decrease in its active transport of rubidium ions. Biochemically, it was assessed by measuring the lowering of adenosine triphosphate and glutathione. The incorporation of pyruvate in the medium protected the lens against these deleterious effects. That the beneficial effect of pyruvate is attributable to its ROS-scavenging property was proven by the peroxide depletion in its presence, commensurate with its own utilization in parallel. A protective effect of this keto acid against UV-induced tissue damage has been shown for the first time, suggesting its clinical usefulness against UV irradiation-induced pathologies. Hence, further studies on the possible protective effects of such alpha-keto acids against UV damage are in progress.     

Practical selection criteria for unenhanced cranial CT in patients with acute headache

We studied clinical predictors of cranial computed tomography (CT) abnormalities in patients with acute or acutely worsened headache. Data were collected from chart review of 333 consecutive patients presenting to an emergency department and who were clinically selected for cranial CT. Patients with a positive neurologic examination were at 10.7 times greater risk for a positive CT than the rest of the sample (p<1.5 – 10⁻¹⁰). Using only neurologic examination to select patients for CT would have missed 30.3% of the positive scans. The amnesia, depressed sensorium, and hypertension variables had CT yields approximating 10% or greater even in the presence of a negative neurologic examination. Together with a positive neurologic examination, these variables detected 87.9% of the patients in this sample with positive scans; their absence had a negative predictive value of 98.0%. Of the four patients with positive scans who would have been missed using this strategy, one was discharged directly from the emergency department anyway and the other three developed positive neurologic examinations within 24 hours. One died of causes unrelated to the intracranial pathology. Positive neurologic examination, hypertension, history of amnesia, or a depressed sensorium provide reasonable initial guidelines to select for CT patients with an acute headache.     

Hyperfractionation in advanced head and neck cancer.

This preliminary study was undertaken to observe tumour response and normal tissue tolerance to hyperfractionation. This study showed encouraging locoregional control rate in advanced head and neck cancer. Responses T4 tumors are poor and are prone to recur. This indicates that probably greater dose is needed to control T4 disease. We used 7920 cGy for T4 and late T3 status tumour. This dose is well tolerated by patients. Control of T4 tumours may further be increased by increasing total dose, but in view of inadequate clear cut numerical data of tissue tolerance derived by L-Q = Linear Quadratic formula which is still under clinical trial, further increase in total dose cannot be overemphasized. Longer follow up is necessary to assess the long term control rate and late tissue reaction. There is a need of randomized controlled clinical trial to compare hyperfractionation and conventional fractionation. In next phase we are undertaking randomized study of twice daily, daily and weekly fractionation in advanced head and neck cancer.     

Lactobacillus acidophilus Induces a Strain-specific and Toll-Like Receptor 2–Dependent Enhancement of Intestinal Epithelial Tight Junction Barrier and Protection Against Intestinal Inflammation

Defective intestinal tight junction (TJ) barrier is an important pathogenic factor of inflammatory bowel disease. To date, no effective therapies that specifically target the intestinal TJ barrier are available. The purpose of this study was to identify probiotic bacterial species or strains that induce a rapid and sustained enhancement of intestinal TJ barrier and protect against the development of intestinal inflammation by targeting the TJ barrier. After high-throughput screening of >20 Lactobacillus and other probiotic bacterial species or strains, a specific strain of Lactobacillus acidophilus, referred to as LA1, uniquely produced a marked enhancement of the intestinal TJ barrier. LA1 attached to the apical membrane surface of intestinal epithelial cells in a Toll-like receptor (TLR)-2–dependent manner and caused a rapid increase in enterocyte TLR-2 membrane expression and TLR-2/TLR-1 and TLR-2/TLR-6 hetero-complex–dependent enhancement in intestinal TJ barrier function. Oral administration of LA1 caused a rapid enhancement in mouse intestinal TJ barrier, protected against a dextran sodium sulfate (DSS) increase in intestinal permeability, and prevented the DSS-induced colitis in a TLR-2– and intestinal TJ barrier–dependent manner. In conclusion, we report for the first time that a specific strain of LA causes a strain-specific enhancement of intestinal TJ barrier through a novel mechanism that involves the TLR-2 receptor complex and protects against the DSS-induced colitis by targeting the intestinal TJ barrier.

Intestinal epithelial tight junctions (TJs) are the apical-most junctional complexes and act as a functional and structural barrier against the paracellular permeation of harmful luminal antigens, which promote intestinal inflammation.¹ The increased intestinal permeability caused by defective intestinal epithelial TJ barrier or a leaky gut is an important pathogenic factor that contributes to the development of intestinal inflammation in inflammatory bowel disease (IBD) and other inflammatory conditions of the gut, including necrotizing enterocolitis and celiac disease.^2,3 Clinical studies in patients with IBD have found that a persistent increase in intestinal permeability after clinical remission is predictive of poor clinical outcome and early recurrence of the disease, whereas normalization of intestinal permeability correlates with a sustained long-term clinical remission.4, 5, 6 Accumulating evidence has found that a defective intestinal TJ barrier plays an important role in exacerbation and prolongation of intestinal inflammation in IBD. Currently, no effective therapies that specifically target the tightening of the intestinal TJ barrier are available.Intestinal microbiota play an important role in modulating the immune system and in the pathogenesis of intestinal inflammation.⁷ Patients with IBD have bacterial dysbiosis in the gut, characterized by a decrease in bacterial diversity and an aberrant increase in some commensal bacteria, which are an important factor in the pathogenesis of intestinal inflammation.^8,9 Normal microbial flora of the gastrointestinal tract consists both of bacteria that are known to have beneficial effects (probiotic bacteria) on intestinal homeostasis and bacteria that could potentially have detrimental effects on gut health (pathogenic bacteria).¹⁰ The modulation of intestinal microflora affects the physiologic and pathologic states in humans and animals. For example, fecal transplantation from healthy, unaffected individuals to patients with refractory Clostridium difficile colitis is curative in up to 94% of the treated patients, and transfer of stool microbiome from obese mice induces obesity in previous lean mice, whereas transfer of microbiome from lean mice preserves the lean phenotype.11, 12, 13 The beneficial effects of gut microbiota are host and bacterial species-specific.¹⁴ Although multiple studies indicate that some commensal bacteria play a beneficial role in gut homeostasis by preserving or promoting the intestinal barrier function, because of conflicting reports, it remains unclear which probiotic species cause a persistent predictable enhancement in the TJ barrier and could be used to treat intestinal inflammation by targeting the TJ barrier. For example, some studies suggest that Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus plantarum, or Lactobacillus rhamnosus cause a modest enhancement in the intestinal epithelial TJ barrier, whereas others have found minimal or no effect of these probiotic species on the intestinal TJ barrier.15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 The major aim the current study was to perform a high-throughput screening of Lactobacillus and other bacterial species to identify probiotic species that induce a rapid, predictable, and marked increase in the intestinal epithelial TJ barrier and protect against the development of intestinal inflammation by preserving the intestinal TJ barrier.In the studies described herein, most of the probiotic species tested (>20 species or strains) had a modest or minimal effect on intestinal TJ barrier function. L. acidophilus uniquely caused a rapid and marked increase in intestinal TJ barrier function. Further analysis indicated that the effect of L. acidophilus was strain-specific, limited to a specific strain of L. acidophilus, and did not extend to other L. acidophilus strains. The L. acidophilus enhancement of the intestinal TJ barrier was mediated by live bacterial-enterocyte interaction that involved Toll-like receptor (TLR)-2 heterodimeric complexes on the apical membrane surface of intestinal epithelial cells. Our animal studies also found that L. acidophilus causes a marked enhancement in mouse intestinal barrier function and protects against the dextran sodium sulfate (DSS)–induced colitis by preserving and augmenting the mouse intestinal barrier function in a strain-specific manner.     

Incidence of Mallophaga on poultry in Dehradun (India).

The order of abundance of different mallophagan species on poultry birds in Dehradun (India) has been found to be Menopon gallinae greater than Menacanthus cornutus greater than Menacanthus stramineus greater than Goniocotes gallinae greater than Goniodes dissimilis greater than Lipeurus caponis greater than Lipeurus lawrensis tropicalis greater than Goniodes gigas. The intensity of these species upon 1249 birds has been recorded by coding system. The correlation between the monthly incidence of different species and environmental temperature as well as R.H. has been recorded. The degree of association between four most commonly occurring combinations has also been analysed.     

Anti-microbial active composite nanoparticles with magnetic core and photocatalytic shell: TiO2-NiFe2O4 biomaterial system

Reverse micelle and chemical hydrolysis techniques have been successfully combined to synthesize composite nanoparticles consisting of a photocatalytic shell of titania and a magnetic core of nickel ferrite. The nature of titania shell, i.e. anatase or brookite, depends on the TiO₂ and NiFe₂O₄ molar ratio. The work presented here describes the photocatalytic and anti-microbial activity of the composite nanoparticles together with the magnetic characteristics of the nickel ferrite core. The TiO₂-coated NiFe₂O₄ nanoparticles retain the magnetic characteristics of uncoated nanocrystalline nickel ferrites (superparamagnetism; absence of hysteresis, remanence and coercivity at 300 K) encouraging their application as removable anti-microbial photocatalyst nanoparticles that can be extracted from the sprayed surface (human body or environment) after exposure.     

Suppressor T cells for delayed-type hypersensitivity to Japanese encephalitis virus.

The delayed-type hypersensitivity (DTH) to Japanese encephalitis virus (JEV) and the suppressor cells controlling it and the antibody-forming cells in inbred Swiss mice have been studied. JEV induces DTH, with a peak response at day 7 following infection which persists at low levels at least up to 119 days. Suppressor activity appeared on day 18. It was transferable by immune spleen cells. Treatment of spleen cells with anti-Thy-1.2 antisera and complement abrogated the suppressor activity. The homogenate of the spleen was equally effective in mediating suppression of DTH and the humoral response as measured by direct antibody plaque-forming cell (IgM-PFC) assay. The suppressor activity was antigen-specific both on DTH and T helper for antibody response as the immune responses against SRBC or Coxsackie B4 virus were not suppressed. The suppressor cells were sensitive to cyclophosphamide treatment when the drug was given 48 hr before their appearance. It is, therefore, concluded that in JEV infection of mice, antigen-specific suppressor T cells are generated, both for DTH and IgM antibody, which are cyclophosphamide-sensitive and mediate suppression through soluble product(s).