Indole-2-carboxylic acid derived mono and bis 1,4-disubstituted 1,2,3-triazoles: Synthesis, characterization and evaluation of anticancer, antibacterial, and DNA-cleavage activities.

A series of new indole-2-carboxylic acid derived mono and bis 1,4-disubstituted 1,2,3 triazoles (I(1)-I(6) and I(7)-I(12)) were synthesized and screened for their anticancer (in vitro and in vivo), antibacterial, and DNA cleavage activities. All the synthesized compounds were characterized by spectral studies. The in vitro anticancer screening results revealed that compound I(12) has registered potential activity against MCF-7, HeLa and HEK293 as compared with the standard reference drug Cisplatin. Remaining compounds have exhibited moderate to good activity against three cancer cell lines. The antibacterial activity screening results revealed that compounds, I(6) and I(12) have registered excellent inhibition against Escherichia coli and Bacillus subtilis in comparison with the standard drug Streptomycin. Compounds I(2) and I(11) have partially cleaved the DNA at 100 µg mL(-1) concentration.

Risk of lymphoma subtypes after solid organ transplantation in the United States.

BACKGROUND: Solid organ transplant recipients have high risk of lymphomas, including non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL). A gap in our understanding of post-transplant lymphomas involves the spectrum and associated risks of their many histologic subtypes. METHODS: We linked nationwide data on solid organ transplants from the US Scientific Registry of Transplant Recipients (1987-2008) to 14 state and regional cancer registries, yielding 791 281 person-years of follow-up for 19 distinct NHL subtypes and HL. We calculated standardised incidence ratios (SIRs) and used Poisson regression to compare SIRs by recipient age, transplanted organ, and time since transplantation. RESULTS: The risk varied widely across subtypes, with strong elevations (SIRs 10-100) for hepatosplenic T-cell lymphoma, Burkitt's lymphoma, NK/T-cell lymphoma, diffuse large B-cell lymphoma, and anaplastic large-cell lymphoma (both systemic and primary cutaneous forms). Moderate elevations (SIRs 2-4) were observed for HL and lymphoplasmacytic, peripheral T-cell, and marginal zone lymphomas, but SIRs for indolent lymphoma subtypes were not elevated. Generally, SIRs were highest for younger recipients (<20 years) and those receiving organs other than kidneys. CONCLUSION: Transplant recipients experience markedly elevated risk of a distinct spectrum of lymphoma subtypes. These findings support the aetiologic relevance of immunosuppression for certain subtypes and underscore the importance of detailed haematopathologic workup for transplant recipients with suspected lymphoma.

Neuroprotective effect of allopurinol and nimesulide against cerebral ischemic reperfusion injury in diabetic rats.

OBJECTIVES: The main objective of the study was to determine the neuroprotective effect of allopurinol and nimesulide against the cerebral ischemic reperfusion injury in diabetic and nondiabetic rats. MATERIALS AND METHODS: In this study, Wistar albino rats of either sex weighing 150-250 g were procured from authorized suppliers. Rats were anesthetized by giving thiopentone sodium (45 mg/kg) by i.p. Under anesthesia, midline incision was given. Common carotid arteries were identified and isolated carefully from vago-sympathetic nerve. Rats were made ischemic by occluding bicommon carotid arteries with thread for 30 min, followed by reperfusion for 4 h by removing the occlusion. The drugs allopurinol (15, 30 mg/kg) and nimesulide (20, 40 mg/kg) were administered 10 min before reperfusion. Then after 4 h reperfusion, animals were sacrificed and immediately brain was removed, homogenized, centrifuged and supernatant was collected, various enzyme estimations were done and same procedure was followed in streptozotocin (STZ: 45 mg/kg; i.p.) induced diabetic rats. RESULTS: Ischemia reperfusion (I/R) group showed significant increase in malondialdehyde (MDA), myeloperoxidase (MPO) and depletion in catalase (CAT) and superoxide dismutase (SOD) levels. Treatment with allopurinol and nimesulide significantly decreased the MDA and MPO levels whereas increased the SOD and CAT levels when compared I/R group in both non-diabetic and diabetic rats. CONCLUSIONS: These findings suggest the cerebral injury due to over production of free radicals was inhibited by allopurinol and nimesulide that exert a neuroprotective effect probably by radical scavenging and antioxidant activities.

Magnesium Hydrogen Phosphate: An Efficient Catalyst for Acrylic Acid Production from Biorenewable Lactic Acid.

A series of Magnesium hydrogen phosphate (MgHP) catalysts with different magnesium to phosphorous (Mg/P) mole ratios at varying calcination temperatures has been synthesised, bearing in mind the effectiveness as well as the stability of MgHP to catalyse acrylic acid (AA) production from biorenewable lactic acid (LA), a synthetic process applicable to biomass conversion. The physicochemical properties of the MgHP catalysts have been thoroughly characterised and the formation of Mg(NH4)PO4, MgHPO4 and Mg2P2O7 with different structural and acidic properties have been reported. The high catalytic performance of MgHP catalysts with high AA yields (100% conversion and 85% selectivity) at high space velocities (WHSVLA = 3.13 h-1) have been achieved at 360 °C. NH3-Temperature programmed desorption (TPD) and pyridine FTIR have shown that the effectiveness of a catalyst is accounted for not primarily by the actual strength of acidic sites, but is due to the presence of Lewis acidic sites compared to Bronsted sites.

Influence of education level on cancer survival in Sweden.

BACKGROUND: While cancer survival at several sites has historically been shown to vary by education level, a current comprehensive assessment of survival following a cancer diagnosis in Sweden, a country with universal health care and cancer screening, has yet to be carried out. METHODS: Using the 2006 update of the Swedish Family-Cancer Database and Cox's proportional hazards regression methods, we calculate the adjusted hazard ratio (HR) and 95% confidence interval to estimate the influence of education level on site-specific cancer survival. RESULTS: Significant positive associations between education level and cancer survival were observed following a diagnosis of upper aerodigestive track cancer, colon cancer, pancreatic cancer, lung cancer, kidney cancer, urinary bladder cancer, melanoma, non-Hodgkin's lymphoma, breast cancer, endometrial cancer, cervical cancer, prostate cancer, and testicular cancer. Although the HRs differed between cancer sites, compared with women and men completing <9 years of education, university graduates were associated with a significant 40% improved survival for all cancer sites combined. CONCLUSIONS: Survival differences by education level were observed for both indolent and aggressive malignancies.

Characterization of CLA-producing Butyrivibrio spp. reveals strain-specific variations.

Conjugated Linoleic Acid (CLA), a fatty acid with high nutraceutical value is produced in rumen by resident bacterial species, especially Butyrivibrio spp. The present study was undertaken to examine the diversity of indigenous Butyrivibrio spp. from rumen liquor of Indian ruminants. The isolates were screened for their CLA production capability at different level of linoleic acid (LA) (0, 200, 400, 600, 800 µg/ml) at different time intervals (0, 2, 4, 6, 12, and 24 h). A total of more than 300 anaerobic cultures were isolated and 31 of them were identified as Butyrivibrio spp. based on morphological, biochemical and molecular characterization. Further, molecular characterization revealed that a large portion (67.7 %) of isolated Butyrivibrio belonged to Butyrivibrio fibrisolvens (B. fibrisolvens) species which is considered to be the most active bacteria amongst the rumen bacteria populace in terms of CLA production. Bacterial isolate VIII (strain 4a) showed highest CLA production ability (140.77 µg/ml) when incubated at 200 µg/ml LA for 2 h, which is 240 % higher than the isolate XXVII, Butyrivibrio proteoclasticus (B. proteoclasticus) showing lowest CLA production (57.28 µg/ml) amongst the screened isolates. It was evident from the observations recorded during the course of experiments that CLA production ability is strain specific and thus did not follow a single pattern. CLA production also varied with time of incubation and concentration of free linoleic acid supplemented in the growth medium. The results of these findings put forward a strain that is high CLA producer and can be further exploited as an additive for enhancing meat and milk quality in ruminants.

Epsilon-aminocaproic acid and recurrent subarachnoid hemorrhage: a clinical trial.

A clinical trial of epsilon-aminocaproic acid (EACA) in preventing recurrent hemorrhage from intracranial arterial aneurysms is reported. Previous reports were reviewed, and their results concerning antifibrinolytic agents were inconclusive in establishing their efficacy. One hundred patients with documented ruptured intracranial aneurysms were admitted to this study within 48 hours of the initial hemorrhage: 45 patients received 36 gm of EACA/day, with 11 documented rebleeds and one suspected rebleed. No benefit was seen from the use of EACA.

Biochemical studies on the age-related toxicity of galactosamine in primary rat hepatocyte cultures.

Galactosamine (GalN) induces liver injury by depletion of uracil nucleotides. The objectives of this study were to investigate the age-related hepatotoxicity of GalN and to find out the mechanism(s) governing this toxicity in primary rat hepatocyte cultures. Hepatocyte cultures were established from foetal (day 20 of gestation), neonatal (3-day), adult (5-month) and aged (30-month) rat livers, and were exposed to 5 mm-GalN 24 hr after seeding. UDP-glucose (UDP-Glc), UDP-galactose (UDP-Gal) and glycogen were measured as indicators of disturbances in uracil nucleotides at 1, 12, 24, 48 and 60 hr after the addition of GalN. Additionally, UDP-glucosamine (UDP-GlcN) and UDP-galactosamine (UDP-GalN) were measured as uracil-trapping metabolites of GalN. Furthermore, the uptake of [(3)H]GalN by hepatocyte cultures of different ages also was determined after incubation of cell cultures with radioactive GalN. UDP-Glc, UDP-Gal and glycogen were decreased significantly at 24, 48 and 60 hr after treatment of adult hepatocyte monolayers. Although the concentrations of UDP metabolites of glucose, galactose and glycogen were decreased in aged liver cells, the decreases were considerably smaller than those in the adult cells. Measurement of the same biochemicals in foetal and neonatal cells did not reveal any significant decrease in their concentrations. The uracil-trapping metabolites, UDP-GlcN and UDP-GalN, were detected at significant concentrations in adult hepatocytes. Although these metabolites were detected in cells of other ages, their levels were significantly lower than in the adult cells. Even though the uptake of [(3)H]GalN by the cells reached a maximum at 30 min in all four ages, it was significantly higher in adult cells followed by aged, foetal and neonatal hepatocytes. A significantly lower uracil trapping by GalN metabolites in foetal and neonatal hepatocytes might be mitigated by further metabolism to non-toxic metabolites by foetal and neonatal cells. This could also be a direct result of much lower GalN uptake by these cells. These studies suggest that the age difference in GalN toxicity demonstrable in vitro may be related to the rate of GalN uptake and further metabolism of uracil-trapping metabolites such as UDP-GlcN and UDP-GalN.

Emergence of non-group A streptococcal necrotizing diabetic foot infections.

Recently the authors have noted a disturbing trend toward an increased incidence of necrotizing infections caused by non-group A streptococcal species. This article describes the typical clinical course of such an infection. Prompt surgical intervention, coupled with an antibiotic regimen aimed at mitigating exotoxin release, may be both limb- and life-preserving.

Vibration perception threshold: are multiple sites of testing superior to single site testing on diabetic foot examination?

Vibration perception threshold (VPT) values, measured at different anatomic locations on the foot and ankle, and the time to assess VPT and sensory perception using two difference modalities in 102 diabetic patients were compared. VPT was evaluated at the great toe, fifth metatarsal and ankle. Differences in VPT at these three sites, in addition to differences in duration of testing comparing single site (great toe) to multiple sites, and to standard SWMF testing were assessed. No significant difference in VPT between the great toe and fifth metatarsal was found for patients both with and without loss of protective sensation (LOPS). Mean VPT was significantly higher at the ankle compared with both the great toes and fifth metatarsals. However, the difference between ankle and great toe was not significant between patients with and without LOPS [3.9 +/- 11.2 (12%) vs. 3.0 +/- 10.8 (16%) volts, respectively, p > 0.6]. Testing of one site took approximately half the time of Semmes-Weinstein 10-gram monofilament wire SWMF testing (40.5 +/- 16.9 vs. 22.3 +/- 9.1 seconds, p < 0.01) and less than one third the time of three-site VPT testing (10.5 +/- 26.1 vs. 22.3 +/- 9.1 seconds, p < 0.01). There may not be a significant practical benefit in multiple site VPT testing when compared with single site testing on the great toe alone. The value of multiple site testing is further called into question when one notes that the great toe VPT remains the only site tested for sensitivity and specificity for ulceration.

Management of opioid-induced pruritus: a role for 5-HT3 antagonists?

We have evaluated the efficacy of ondansetron in the prevention of opioid-induced pruritus in a prospective, randomized, double-blind, placebo-controlled study. Using a 'human model' of opioid-induced pruritus, 80 ASA I-II patients about to undergo routine surgery were given either ondansetron 4 mg i.v. or 0.9% saline i.v. (40 in each group), 30 min before alfentanil 10 mg kg-1 i.v. During the following 5 min, patients were observed for signs of perinasal scratching and at 5 min were asked about symptoms of pruritus. The study was then terminated and anaesthesia was induced. There was a significant reduction in the incidence of scratching in patients receiving ondansetron compared with placebo (42.5% vs 70%, respectively, P = 0.013). The incidence of itching in the ondansetron group was less than that in the placebo group but this was not statistically significant (30% vs 42.5%, respectively, P = 0.245). We conclude that the 5-HT3 antagonist ondansetron may have a role in the management of opioid-induced pruritus.

Air quality status at selected locations in Hyderabad City.

A case study for assessing the air quality status is elaborated for Hyderabad city. Monitoring was carried out at 11 locations during March 2003. These observations on air quality status and AQEI predicts that most of the localities in Hyderabad are experiencing the air pollution stress and the trend is likely to worsen in near future if proper control measures are not implemented.

Studies on the age-dependent effects of galactosamine in primary rat hepatocyte cultures.

Galactosamine (GalN) has been known to induce liver injury by depletion of uracil nucleotides. The objective of the present work was to examine age-dependent toxicity of GalN in primary hepatocyte cultures. Hepatocytes from fetal (Day 20 of gestation), neonatal (2.5-day), adult (5-month), and aged (30-month) rats were established as monolayered cultures. LDH leakage, cell viability, UTP, UDP, and UMP were measured as end points of toxicity in cultures exposed to 5 mM GalN. LDH leakage was increased and cell viability was decreased in adult rat hepatocytes at 48 and 60 hr after treatment. Although similar effects were observed in hepatocytes from aged rats, these cells appeared resilient to GalN toxicity as indicated by significantly less LDH leakage and cell death. Fetal and neonatal rat hepatocytes also exhibited greater resiliency to GalN based on the same end points. The UTP, UDP, and UMP levels of aged hepatocytes (30-month) were higher than control adult levels to begin with and dropped after GalN treatment. The level of UMP at 60 hr was similar to that of normal adult cells, but the UTP and UDP levels were significantly higher in aged hepatocytes in comparison to those of adult hepatocytes. The levels of uracil nucleotides in the fetal and neonatal cells were the same as those in adult cells, but did not decrease significantly after exposure to GalN. These findings show that aged rat hepatocytes have a higher set point for uracil nucleotides, which is consistent with the relative resiliency of these cells to GalN injury. Neonatal and fetal cells have the same set point for these nucleotides as adult rats, but are relatively resistant to GalN-induced depletion. In conclusion, the differences in toxicity of GalN may reside in age-related differences in the regulation of uracil nucleotide biochemistry.

Ongoing hepatocellular regeneration and resiliency toward galactosamine hepatotoxicity.

In previous studies, we reported that the age-dependent hepatotoxicity of galactosamine (GalN) was evident in hepatocytes maintained in primary cultures. Cellular proliferation and tissue repair are not manifested in response to injury in this in vitro system. Neonatal (5-day) rats have ongoing hepatocellular proliferation in contrast to adult (5-month) rats, and should be therefore resilient to GalN toxicity. Liver injury was assessed by serum transaminases (ALT, AST), 3H-thymidine (3H-T) incorporation into nuclear DNA, and content of hepatocellular nuclear DNA. While the dose of 400 mg/kg did not cause any significant liver injury in the neonates, it did produce significant liver injury in adult rats. At a dose of 800 mg/kg, GalN produced significant injury in the neonates. Because 400 mg/kg causes clearly demonstrable liver injury in the adult and no injury in the neonates, this dose was used for further studies. In addition to the above measures of injury, uracil nucleotides (UTP, UDP, and UMP), glycogen, histopathology, and autoradiographic examination of liver sections were used to assess the liver injury in neonatal and adult rats. In a time-course study, all of the above were measured at 0, 12, 24, 36, 48 and 72 h after GalN administration. Serum enzyme elevations as well as the appearance of necrotic and swollen hepatocytes were maximal at 24 h in the adults rats. In contrast to these observations in the adult rats, none of these measurements indicated significant liver injury in the neonates. 3H-T incorporation into nuclear DNA was much higher in the neonatal liver in comparison to the adults reflecting the difference in regeneration. Hepatocellular nuclear DNA was also higher in the neonate and was significantly decreased due to GalN treatment. In the adult rats, the quiescent normal level of 3H-T incorporation and nuclear DNA content were further decreased at 12 h, increased at 48 h and returned to normal low, quiescent levels at 72 h. In the neonates mitotic activity of hepatocytes was higher than in the adult rats. In the adult rats, mitotic activity was increased at 48 h after GalN administration and returned to normal at 72 h. In the neonates GalN did not alter the mitotic activity significantly. These findings demonstrate that in the presence of hepatocellular regeneration, galactosamine toxicity is minimal while in the absence of it, clear toxicity is manifested. In conclusion, while perturbation in uracil nucleotides and related biochemical events may explain the infliction of liver injury by GalN in an age-dependent fashion, the extent of tissue repair impacts decisively on the final outcome of injury.