Potent synergistic combination of rosuvastatin and levofloxacin against Staphylococcus aureus: in vitro and in vivo study.

AIMS: The present study aims to evaluate the capability of rosuvastatin to synergize with levofloxacin against Staphylococcus aureus. METHODS AND RESULTS: Rosuvastatin inhibited the growth of S. aureus with minimum inhibitory concentration of 16 µg ml-1 . Additionally, it showed a bactericidal effect at 4x minimum inhibition concentration. Using a checkerboard method, a synergistic effect was recorded when rosuvastatin was combined with levofloxacin showing against S. aureus isolate 28 (S 28). Furthermore, this combination was also able to display a significant reduction in biofilm formation (92·8%) and suppress the production of coagulase and ß-haemolysin, and virulence factors of S. aureus isolate 28. An animal model for wound infection was used to assess the therapeutic effect of the test combination, in vivo. It was found that the test combination reduced the bacterial burden in the infected wounds by 91·3%. Pathological and histological analyses have revealed a decline in cell infiltration in the excisional wound skin tissue after treatment with rosuvastatin and levofloxacin combination. CONCLUSIONS: Rosuvastatin combined with levofloxacin can be considered as a promising solution to combat S. aureus antibiotic resistance phenomenon. SIGNIFICANCE AND IMPACT OF THE STUDY: This study unveils the potential effect of rosuvastatin when used in combination with levofloxacin can be used as a topical antibacterial agent to treat S. aureus skin infections.

Molecular understandings on 'the never thirsty' and apomictic Cenchrus grass.

The genus Cenchrus comprises around 25 species of 'bristle clade' grasses. Cenchrus ciliaris (buffel grass) is a hardy, perennial range grass that survives in poor sandy soils and limiting soil moisture conditions and, due to the very same reasons, this grass is one of the most prevalent fodder grasses of the arid and semi-arid regions. Most of the germplasms of Cenchrus produce seeds asexually through the process of apomeiosis. Therefore, the lack of sufficient sexual lines has hindered the crop improvement efforts in Cenchrus being confined to simple selection methods. Many attempts have been initiated in buffel grass to investigate the various molecular aspects such as genomic signatures of different species and genotypes, molecular basis of abiotic stress tolerance and reproductive performance. Even though it is an important fodder crop, molecular investigations in Cenchrus lack focus and the molecular information available on this grass is scanty. Cenchrus is a very good gene source for abiotic stress tolerance and apomixis studies. Biotechnological interventions in Cenchrus can help in crop improvement in Cenchrus as well as other crops through transgenic technology or marker assisted selection. To date no consolidated review on biotechnological interventions in Cenchrus grass has been published. Therefore we provide a thorough and in depth review on molecular research in Cenchrus focusing on molecular signatures of evolution, tolerance to abiotic stress and apomictic reproductive mechanism.

Standardized modulation of the injection site allows for insulin dose reduction without deterioration of metabolic control.

OBJECTIVES: Use of an injection site modulation device (InsuPad) in intensive insulin treatment reduces frequency of hypoglycemia and prandial insulin requirements by enhancing subcutaneous microcirculation. This meal tolerance test (MTT) investigation was performed as a sub-study during the real-world BARMER study to demonstrate non-inferiority of the reduced insulin doses observed in this study with respect to metabolic control. METHODS: The MTT was performed at baseline and after 3 months in insulin treated diabetes patients using the modulation device vs. a control group without device. The dose used for the MTT was individually calculated based on the prandial insulin records from the patient diaries before the test. Blood was drawn for determination of glucose, insulin, C-peptide, proinsulin, triglycerides, free fatty acids, nitrotyrosine, and asymmetric dimethyl-arginine (ADMA) at multiple time-points from 0 to 300 min. A total of 32 patients from one site were included into this MTT study (8 female, 7 type 1 diabetes, age: 49.9 ± 12.5 yrs, HbA1c: 7.2 ± 0.5%). RESULTS: During the BARMER study, mean HbA1c was treated to target (<6.5%) in both groups. The prandial insulin dose decreased in the MTT modulation device group by -17.1%, but remained unchanged in the control group (-0.1%, p < 0.001). No change was seen for the basal insulin dose in both treatment arms. There were no differences between the groups with respect to the postprandial curves for glucose, C-peptide, intact proinsulin, free fatty acids, and triglycerides. Insulin absorption was faster with the modulation device (Tmax: 60 ± 28 min vs. 99 ± 46 min, p < 0.05). Key limitations are the small patient sample size and impossibility to determine the short-term effects of device use. CONCLUSIONS: The results of this meal tolerance sub-study confirm that the observed prandial insulin dose reduction when using the injection site modulation device has no negative impact on postprandial metabolism.

The Barmer study: impact of standardized warming of the injection site to enhance insulin absorption and reduce prandial insulin requirements and hypoglycemia in obese patients with diabetes mellitus.

BACKGROUND: The primary objective of this prospective controlled study was to investigate the impact of standardized injection-site warming on prandial rapid acting insulin dose and glycemic control when studied under real-world conditions. METHODS: All 145 participating patients (51 female, 94 male, 13 type 1 and 132 type 2 patients, age: 61.6 ± 8.4 yrs, HbA1c: 7.19 ± 0.50%) were treated with intensive insulin glargine and short-acting insulin analog therapy. After a 4 week treatment optimization run-in period, patients were randomized to continue therapy for three months without (control) or with a local injection-site warming device (InsuPad * ). Observation parameters included HbA1c, insulin dose, frequency of hypoglycemia, body weight and adverse events. RESULTS: HbA1c improved in both arms until study end (control group: 6.3 ± 0.5%; injection-site warming device: 6.3 ± 0.5%; both p < 0.001 vs. baseline). To achieve this good control, patients in the control group needed to increase the daily prandial insulin dose by 8.1% (from 66 ± 31 U to 71 ± 38 U, p < 0.05) with stable basal insulin requirements. Patients who used the injection-site warming device required less prandial insulin (70 ± 43 U to 55 ± 34 U; -19%, p < 0.001) and slightly more basal insulin (+3.9%). Total daily insulin dose increased in the control group (+3.7%) and decreased with warming device use (-8.6%, p < 0.001). The number of hypoglycemic events (<63 mg/dL) during the observation period was higher in the control group (6.2 ± 9.9/patient vs. injection-site warming device: 3.3 ± 4.8/patient, p < 0.05). Main study limitations can be seen in the open label design reliability of the collected dose information and the very obese patient cohort. CONCLUSION: When treating obese patients to target with insulin therapy, use of an injection-site warming device for 3 months resulted in a lower frequency of hypoglycemic events and a reduction in prandial insulin analog requirements. If these results are confirmed in other patient populations, an injection-site warming device may be useful in achieving treatment targets with a safer and more efficient basal bolus therapy in insulin-treated patients with type 1 and type 2 diabetes.

Profile and treatment outcomes of elderly patients with tuberculosis in Delhi, India: implications for their management.

BACKGROUND: Given India's high rate of TB, rising burden of non-communicable diseases (NCDs) and growing elderly population, elderly TB patients may be at higher risk of adverse outcomes including death, loss-to-follow-up (LTFU) and treatment failure. This may call for modifications in their management. This study thus aimed to compare the profile and treatment outcomes between elderly (≥60 years) and non-elderly (15-59 years) TB patients. METHODS: This was a retrospective cohort study using routinely-collected programme data from a chest clinic in Delhi, India. It included all elderly and selected non-elderly TB patients registered for treatment between 2005 and 2010. Data on patients' clinical and demographic characteristics and treatment outcomes were analysed. RESULTS: There were 812 elderly and 1624 non-elderly TB patients. Elderly patients were more likely to be male (63.2% vs 51.1%) and have smear-positive TB (56.0% vs 47.4%). Adverse outcomes were more frequent among elderly patients (adjusted OR 1.9, 95% CI: 1.5-2.4), specifically deaths (adjusted OR 5.0, 95% CI: 3.1-8.1) and lost-to-follow-up (adjusted OR 1.4, 95% CI: 1.0-1.9). CONCLUSIONS: The profile and worse outcomes of elderly Indian TB patients may be indicative of co-existing NCDs. This needs further investigation and likely calls for a more comprehensive and intensive approach to their management.

Effect of cooking, fermentation, dehulling and utensils on antioxidants present in pearl millet rabadi - a traditional fermented food.

Effect of cooking, fermentation, dehulling and the use of utensils on flavonoids (quercitin and pelargonidin) - antioxidants present in pearl millet (Pennisetum typhoideum) rabadi, along with proximate composition and sensory acceptability of the product were studied. Study revealed an increased ash and flavonoids and reduced crude fibre after cooking in all samples, while fermentation enhanced the crude protein and reduced fat and crude fibre after 16 h in fermented-cooked-fermented rabadi prepared in steel and earthen pot and cooked-fermented rabadi in earthen pot. Enhanced flavonoids were observed in all samples after 16 h fermentation. Fermented-cooked-fermented samples were better with high (ρ<0.05) protein in steel pot rabadi and high (ρ<0.001) ash and quercitin (ρ<0.1 in earthen pot rabadi. Major nutrients were unaffected after dehulling except the crude fibre, which decreased and quercitin increased significantly (ρ<0.1). Remarkable rise in quercitin was observed when rabadi was fermented-cooked and fermented in earthen pot. Sensory evaluation showed the acceptance of all samples in the range of liked extremely (fermented-cooked-fermented-steel pot) to liked slightly (fermented-cooked in earthen pot).

Effect of pretreatment with chromium picolinate on haematological parameters during dengue virus infection in mice.

BACKGROUND & OBJECTIVE: Dengue virus (DV) has caused severe epidemics of dengue fever (DF) and dengue haemorrhagic fever (DHF) and is endemic all over India. We have earlier reported that exposure of mice to hexavalent chromium [Cr(VI)] compounds increased the severity of dengue virus infection. Trivalent chromium picolinate (CrP) is used worldwide as micronutrient and nutritional supplement. The present study was therefore, carried out to investigate the effects of CrP on various haematological parameters during DV infection of mice. METHODS: The Swiss Albino smice were inoculated with dengue virus (1000 LD50, intracerebrally) and fed with chromium picolinate (CrP) in drinking water (100 and 250 mg/l) for 24 wk. Peripheral blood leucocytes and other haematological parameters, and spleens were studied on days 4 and 8 after virus inoculations and the findings were compared with those given only CrP and the normal control age matched mice. RESULTS: CrP in drinking water for 24 wk had no significant effects on peripheral blood cells of mice. On the other hand, there was significant decrease in different haematological parameters following inoculation of normal mice with DV. In CrP fed mice the effects of DV infection were abolished on most of the haematological parameters. INTERPRETATION & CONCLUSION: The findings of present study showed that the adverse effects of DV infection, specially on platelets and leucocytes, were abrogated by pretreatment of mice with CrP. The therapeutic utility of CrP in viral infections including dengue needs to be studied in depth.

Primary hydatid cyst of neck muscles.

Primary hydatid disease of muscle is very rare. This was encountered in the muscles of posterior triangle of the neck in a 12-year-old boy. Hydatid Cyst of neck was excised and was followed by albendazole for six weeks. Rarity of this disease in muscles warrants the need for this case report.

Effect of mercuric chloride on testicular activities in mice, Musculus albinus.

Impaired testicular function was observed after an exposure of Swiss albino mice (30 +/- 2 g) to mercuric chloride. A sublethal chronic exposure (0.5 ppm for 21 days) resulted in regressed histological and histochemical properties of the testis. The changes observed were degenerated tunica albuginea, abnormal configurations of seminiferous tubules, deformed primary and secondary spermatocytes, hypertrophy and vacuolization in interstitial cells and Sertoli cells. The 3 beta and 17 beta hydroxy steroid dehydrogenase enzyme and the level of testosterone hormone were significantly (p < 0.001) reduced. The diameter of different spermatogenic cells were significantly (p < 0.001) reduced.

Levels of beta-carotene and effects of processing on selected fruits and vegetables of the arid zone of India.

Some locally available fruits and vegetables of the arid zone of Rajasthan were analyzed for their beta-carotene content; the selected fruits and vegetables were: Dansra (Rhus myserensis), Kachri (Cucumis collosus), fruit Kachri (Cucumis collosus), Kair (Capparis decidua) and Sanghri (Prosopis cineriria). The beta-carotene contents of the samples were estimated in fresh and various processed states (blanched, dried and roasted). The results showed the heat lability of beta-carotene. Among the samples, kair was found to be the richest source of beta-carotene. Variety, too, had an impact on the content of this fat soluble vitamin.

Lipoprotein(a) in coronary heart disease: a case-control study.

To determine the significance of lipoprotein(a) levels in coronary heart disease patients, a case-control study was performed with 48 newly diagnosed coronary heart disease patients and 23 controls who were evaluated using clinical history and biochemical examination. Lipoprotein(a) was measured by quantitative latex-enhanced immunoturbidimetric method. Geometric means of biochemical parameters were obtained. Comprehensive lipid tetrad index was calculated using a previously validated formula. There was no significant difference in prevalence of diabetes, hypertension and smoking in cases and controls. Dietary intake of calories, fats, fatty acids and antioxidant vitamins was also similar. The levels of fasting glucose, cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides were not significantly different in cases and controls (p > 0.05). Low-density lipoprotein/high-density lipoprotein ratio (4.33 +/- 1.5 vs 4.29 +/- 1.8) and total cholesterol/high-density lipoprotein ratio (6.59 + 1.7 vs 6.69 +/- 2.2) were similar. The mean lipoprotein(a) levels were significantly greater in cases (11.95 +/- 2.8 mg/dL, range 1-102 mg/dL) as compared to controls (6.68 +/- 3.4 mg/dL, range 1-73 mg/dL) (t = 2.08, p = 0.041). As compared to controls, in coronary heart disease cases, mean lipoprotein(a) levels in patients upto 50 years (10.27 +/- 2.8 vs 7.27 +/- 3.4 mg/dL) as well as those over 50 years (12.99 +/- 2.9 vs 4.91 +/- 3.5 mg/dL) were significantly more (p < 0.05). Coronary heart disease patients had a slightly greater prevalence of high lipoprotein(a) levels, 20 mg/dL or more (31.3 vs 13.0%; chi 2 = 2.83, l-tailed p < 0.05). Comprehensive lipid tetrad index (total cholesterol x triglycerides x lipoprotein(a) divided by high-density lipoprotein cholesterol) was also slightly higher in cases (14688.2 +/- 3.6) than in controls (8358.2 +/- 4.3) (t = 1.68, 1-tailed p < 0.05). This study shows that lipoprotein(a) levels are significantly more in both younger and older coronary heart disease patients as compared to controls.

Role of interleukin-12 in patients with dengue hemorrhagic fever.

Interleukin (IL)-12 has a broad range of activities including regulation of cytokine synthesis and selective promotion of Th1-type cell development. A shift from a Th1-type response to Th2-type has been suggested to be important in the pathogenesis of dengue hemorrhagic fever (DHF). This study was undertaken to investigate the possible role of IL-12 in this shift. A total of 76 patients with various grades of dengue illness and 21 normal healthy controls were tested for IL-12 levels in serum samples and IL-12 mRNA in their peripheral blood mononuclear cells. The results showed that the levels of IL-12 were the highest in patients with dengue fever (270+/-102 pg ml(-1)) followed by decreasing levels in the patients with DHF grade I (198+/-86 pg ml(-1); P<0.05) and DHF grade II (84+/-52 pg ml(-1); P<0.001). Neither IL-12 nor its mRNA could be detected in the patients with DHF grades III and IV. The cytokine appeared and reached peak levels during the first 4 days of illness, started to decline by day 5-8 and disappeared by day 9 onwards. The absence of IL-12 during severe illness and late phases of the disease may be responsible for the shift to a Th2-type response and thus for the pathogenesis of DHF.

Dietary and serum iron, body iron stores and coronary heart disease.

OBJECTIVES: To determine the role of body-iron stores as measured by serum iron, total iron binding capacity (TIBC), transferrin, ferritin and ferritin:transferrin ratio (FTR) in patients with coronary heart disease (CHD). METHODS: A case-control study was performed in 58 newly diagnosed CHD patients and 24 controls who were evaluated using clinical history, dietary history and biochemical examination. Dietary iron was determined by history; serum iron and TIBC were measured biochemically and ferritin by enzyme-linked immunoassay. Case-control comparisons were performed by non-parametric Mann-Whitney test. RESULTS: There was no significant difference in mean age, prevalence of diabetes, hypertension and smoking, and dietary intake of calories and fats in cases and controls. Dietary iron intake was 11.2 +/- 3.4 mg/day in cases and 11.3 +/- 3.8 mg/day in controls (p > 0.05). Serum fasting glucose, cholesterol, LDL cholesterol, HDL cholesterol and triglycerides were not significantly different in cases and controls (p > 0.05). LDL/HDL ratio (4.17 +/- 1.4 vs. 4.62 +/- 2.3) and total cholesterol/HDL ratio (6.47 +/- 1.6 vs. 6.91 +/- 2.4) were also similar. In the whole study group serum iron (54.8 +/- 35.7 mcg/dl), transferrin (11.6 +/- 7.4%) and ferritin (52.4 +/- 57.8 ng/ml) levels were low. In cases as compared to controls serum iron (56.9 +/- 31 vs. 49.6 +/- 45 mcg/dl; z = 1.707, p = 0.088) and transferrin saturation (12.5 +/- 7.8 vs. 9.5 +/- 6.2%; z = 1.83, p = 0.066) were slightly more. Ferritin levels (48.8 +/- 55 vs. 60.9 +/- 64 ng/ml; z = 2.048, p = 0.040) as well as FTR (5.51 +/- 8.6 vs 7.47 +/- 6.1, z = 2.054, p = 0.040) was significantly lower in cases. CONCLUSIONS: In Indian CHD patients the body iron stores are lower as compared to controls.

Profile of transforming growth factor-beta 1 in patients with dengue haemorrhagic fever.

The pathogenesis of dengue haemorrhagic fever (DHF) is incompletely understood but it has been suggested that various cytokines may have a role in the process. In this study the profile of the cytokine Transforming Growth Factor-beta 1 (TGF-beta1) was investigated in the sera of 79 patients with various grades of dengue illness and in 21 normal healthy controls. Also, TGF-beta1-specific mRNA was examined in their peripheral blood mononuclear cells (PBMC). The results showed that neither TGF-beta1 protein nor its mRNA were detected in healthy controls. In dengue patients, the TGF-beta1 protein and its mRNA were detected in 96%. However, among the patient groups, the levels of TGF-beta1 were lowest in patients with dengue fever (DF; mean value 315 +/- 95 pg/ml) and were highest in patients with DHF grade IV (mean value 1350 +/- 280 pg/ml; P = < 0. 001). The cytokine appeared during the first four days of illness (304 +/- 90 pg/ml) and gradually increased, reaching peak levels (1050 +/- 215 pg/ml) after the 9th day of the illness. Thus TGF-beta1 in the sera and TGF-beta1-mRNA in the PBMC were present in most of the patients with dengue (96%) but the cytokine levels were highest during the later periods of illness and in patients with DHF grade IV, suggesting a possible role of TGF-beta1 in the pathogenesis of DHF.

Sequential production of cytokines by dengue virus-infected human peripheral blood leukocyte cultures.

The study was undertaken to elucidate the sequence of appearance of T helper (Th)1- and Th2-type cytokines in human peripheral blood leucocyte cultures infected in vitro with dengue type 2 virus. Commercial sandwich enzyme-linked immunosorbent assay kits were used to assay the levels of tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin (IL)-2, IL-4, IL-5, IL-6, and IL-10 in culture supernatants. Culture supernatants were also screened for the cytotoxic factor and the dengue virus titres determined. The cytokines that appeared in the culture supernatants on the first day post-infection (p.i.) were cytotoxic factor, TNF-alpha, IL-2, and IL-6; their levels were highest on the second day p.i. IFN-gamma appeared on the second day with a peak on the third day p.i. The levels of these cytokines declined quickly, except for human cytotoxic factor (hCF) and IL-2. The cytokines that appeared later were IL-10 and IL-5 on the fourth day and IL-4 on the sixth day p.i. Dengue virus replicated in the peripheral blood leucocyte (PBL) cultures and was present throughout the course of the study. The findings of the present study show that dengue virus induced a predominant Th1-type cytokine response during the first 3 days of infection of PBL cultures that was replaced by a Th2-type response later.

A clinical study of the patients with dengue hemorrhagic fever during the epidemic of 1996 at Lucknow, India.

This paper describes the clinical findings in 206 patients with dengue fever (DF) or with dengue hemorrhagic fever (DHF) during the epidemic of 1996 at Lucknow. The age group affected most was 11 to 30 years and 21% of the patients were less than 10 years old. The male:female ratio was 1.9:1. The onset was abrupt in all the patients, severe frontal headache was observed in 97%, myalgia in 90%, skin rash in 40%, vomiting in 29% and arthralgia in knee and hip joints in 9%. Anuria was seen in two patients. Lymphadenopathy was noted in 14%, hepatomegaly in 4%, being associated with mild jaundice in one patient, and splenomegaly in 2% of the patients. Involvement of the heart and lungs was seen in one patient each and no case with encephalitis was recorded. Hemorrhages from various sites were observed in 54% patients and 17 patients had profound shock. The commonest bleeding site was gums. Profound shock was preceded by various warning signs, the commonest being sudden hypotension. Among the patients with profound shock the mortality was 47% while the overall fatality rate was 3.8%. A number of the risk factors existed for a long time in this part of the world, but what precipitated the present epidemic at this time, is not known.