Limitations of amorphous content quantification by isothermal calorimetry using saturated salt solutions to control relative humidity: Alternative methods

Despite the high sensitivity of isothermal calorimetry (IC), reported measurements of amorphous content by this technique show significant variability even for the same compound. An investigation into the reasons behind such variability is presented using amorphous lactose and salbutamol sulfate as model compounds. An analysis was carried out on the heat evolved as a result of the exchange of water vapor between the solid sample during crystallization and the saline solution reservoir. The use of saturated salt solutions as means of control of the vapor pressure of water within sealed ampoules bears inherent limitations that lead in turn to the variability associated with the IC technique. We present an alternative IC method, based on an open cell configuration that effectively addresses the limitations encountered with the sealed ampoule system. The proposed approach yields an integral whose value is proportional to the amorphous content in the sample, thus enabling reliable and consistent quantifications. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 2080–2089, 2010     

Erythroid development of the FDCP-Mix A4 multipotent cell line is governed by the relative concentrations of erythropoietin and interleukin 3

Summary .Conditions are described which promote the erythroid development of the FDCP-Mix A4 (A4) cell line with accompanying proliferation of the cells. The requirements for this development are low concentrations of interleukin 3 (IL-3) plus the presence of erythropoietin (epo) and haemin. When high concentrations of IL-3 are added with erythropoietin and haemin the cells do not differentiate and maintain their blast cell morphology. Addition of haemin, in the absence of erythropoietin, does not promote erythroid development, but the presence of haemin with erythropoietin promotes increased proliferation and maturation. The morphological maturation of A4 cells along the erythroid lineage is accompanied by a gradual loss of clonogenic potential, loss of A4 cell multipotency, increased erythropoietin receptor expression, and an increased expression of the β-globin gene. An initial increase in mitogenic responsiveness to erythropoietin is followed by a decrease as the cells become refractory to all mitogenic stimuli with the acquisition of a postmitotic, mature erythroid cell phenotype.     

Characterization of two different mucolipin-like genes from Leishmania major

Here, we report the existence of two different mucolipin-like genes in Leishmania parasites. The Leishmania major mucolipin-like A and B genes (lmmlA and lmmlB) encode two proteins of 776 and 590 amino acids, respectively, and may be classified among the mucolipins family [transient receptors potential mucolipin (TRPML)] because (1) they include a large region that exhibits significant similarities with specific domains of ion transport proteins and transient receptors potential (TRP) channels, (2) they contain at least 173 residues that display significant homologies with conserved regions of different mucolipins from several species, and (3) as TRPMLs, they include six predicted transmembrane domains. Gene expression analysis reveals that lmmlB is upregulated in metacyclics and amastigotes relative to procyclics, while lmmlA is constitutively expressed in the three Leishmania developmental stages. These genes could constitute potential drug targets.     

Effectiveness of a 308-nm excimer laser in treatment of vitiligo: a review

Vitiligo is a relatively common acquired disorder, characterized by progressive loss of melanocytes from the epidermis and the epidermal appendages. The disease is associated with considerable morbidity because of a major impact on the quality of life. The treatment for vitiligo is generally unsatisfactory and challenging. There are a variety of therapeutic possibilities including topical corticosteroids, topical calcineurin inhibitors, as well as phototherapy with Psoralen plus UVA (PUVA), narrow-band UVB, and a 308-nm excimer laser and/or lamps. Furthermore, surgical methods encompass grafting and transplantation while depigmentation treatments and psychological support may also be considered. The objective is to assess the effect of the 380-nm excimer laser in the treatment of vitiligo based on the available studies and case series. We searched the relevant literature about vitiligo and excimer laser published between 1990 and 2012 using the MEDLINE database. We reviewed all relevant articles about 308-nm excimer laser and light sources assessing their efficacy in the management of vitiligo as well as their side effects. The value of combination treatment methods was also analyzed. The available studies provide strong evidence that the excimer laser represents the most effective approach to treat vitiligo compared to ordinary phototherapy. Excimer laser is relatively safe and effective for localized disease. UV-sensitive areas respond best as well as a short duration of the disease. More frequent treatments achieve better results. Compared to other treatment modalities, the excimer laser most likely constitutes the treatment of choice for localized vitiligo. Its efficacy can be further improved in combination with other therapies such as corticosteroids, pimecrolimus, or tacrolimus.     

Enhanced urinary trypsin inhibitory activity in gentamicin-induced nephrotoxicity in rats

We delineated in rats, the relationship between trypsin inhibitory activity in the urine and the nephrotoxic effects of gentamicin, eg, proteinuria and deterioration of glomerular filtration rate (GFR), measured by creatinine clearance. Gentamicin, 70 mg/kg per day, was injected intraperitoneally for 6-10 successive days. Serum and urine gentamicin levels were determined by a microbiological test. Trypsin inhibitory activity was assayed by the casein digestion method. The results showed a steady increase in urinary trypsin inhibitory activity starting from the fourth injection day. The increased levels of urinary trypsin inhibitory activity were associated with increased levels of urinary gentamicin excretion (r = 0.36, p less than 0.02, n = 50 after the fourth injection day), and were significantly higher than in control groups (p less than 0.001). The urinary trypsin inhibitory activity was inversely correlated with the GFR (r = -0.45, p less than 0.01, after the second injection day). The serum trypsin inhibitory activity remained unchanged throughout the study period in all groups. These data suggest that increased urinary trypsin inhibitory activity may be involved in the pathogenesis of gentamicin-induced nephrotoxicity.     

Hydrolysis of Cellulose Rich Agricultural Waste Using Two Potent Local Bacterial Isolates

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Cellulolytic enzymes have received a lot of attention as prospective candidates for biomass conversion of...     

Antimicrobial gentamicin activity in the presence of exogenous protease inhibitor (Bowman-Birk inhibitor) in gentamicin-induced nephrotoxicity in rats.

In our previous studies, we found increased levels of urinary trypsin inhibitory activity in gentamicin-induced nephrotoxicity in rats. Following administration of the Bowman-Birk trypsin and chymotrypsin inhibitor (BBI), no proteinuria was detected in gentamicin-treated rats, and a decrease in creatinine clearance was noted in only 50% of the injected rats. In the present study, we examined the antimicrobial activity of gentamicin against Escherichia coli in the presence of BBI in gentamicin-induced nephrotoxicity in rats. We found that 50% of rats with E. coli-positive blood cultures died of septicemia. All the rats injected with E. coli plus gentamicin or E. coli plus gentamicin plus BBI survived, the latter showing no proteinuria or deterioration in creatinine clearance. In conclusion, BBI, which is an effective inhibitor of gentamicin-induced nephrotoxicity, does not affect the antimicrobial activity of gentamicin sulfate.     

Étude comparative de la protéine C-réactive et de la procalcitonine dans le diagnostic de sévérité des pyélonéphrites aiguës de l’enfant

ObjectiveThe aim of this study is to compare two biologic parameters; C-reactive protein (CRP) and procalcitonin (PCT) in the detection of acute renal lesions assessed by DMSA scintigraphy in the urinary tract infection in child.DesignIn a prospective study, serum PCT, CRP and leukocyte counts were measured for children admitted, between January and December 2010, with a first episode of febrile urinary tract infection.ResultsSeventy-five children were enrolled in the study. Thirty-three patients had renal lesions (group A) and 42 had a normal DMSA scintigraphy (group B). The mean PCT level was significantly higher in group A than in group B (8.81 ng/mL versus 1.7 ng/mL, P = 0.01). In this study, using receiver operating characteristic (ROC) curve, we identified that the optimal cut-off value with ideal sensitivity and specificity for PCT in detection of renal lesions was 0.76 ng/mL and for CRP, it was 70 mg/L. The sensitivity, the negative predictive value and the indice of Youden of the cut-off value of PCT were significantly higher than CRP (82% versus 70%; 84% versus 70% and 0.58 versus 0.25).ConclusionsThis study confirmed that the serum PCT level was more sensitive and specific than the CRP in the detection of renal lesions in the first urinary tract infection in child.     

Prophylactic etoricoxib is effective in preventing "first of Ramadan" headache: a placebo-controlled double-blind and randomized trial of prophylactic etoricoxib for ritual fasting headache

Background.— Religious fasting is associated with headache. This has been documented as “Yom Kippur headache” and “first of Ramadan headache.” Etoricoxib, a Cox‐2 inhibitor with a 22‐hour half‐life, has been shown effective in preventing fasting headache when taken just prior to the 25‐hour Yom Kippur fast. We hypothesized that etoricoxib would also be effective in preventing headache during Ramadan, despite the different characteristics of the fast. Methods.— We performed a double‐blind randomized prospective crossover trial of etoricoxib 90 mg vs placebo, taken just prior to the onset of fasting, during the first 2 weeks of Ramadan 2010. Healthy adults aged 18‐65 years were enrolled. Demographics, headache history and a daily post‐fast survey were collected. We compared incidence, time of onset, and intensity of headache on each day and side effects in control and treatment groups. Results.— We enrolled 222 patients and 189 completed the post‐fast questionnaire (87%). Etoricoxib reduced the incidence of “first of Ramadan” headache by 54% (46% in placebo group [n = 92] vs 21% [n = 96] in etoricoxib group) (P < .0001, OR 3.19 [95% CI 1.68‐6.06]). For days 1‐6, the mean number of headache days for the placebo group was 1.60 (n = 92) and for the treatment group the mean was 0.86 (n = 99) headache days (P = .003). Median severity of headache in the treatment group was significantly lower. In the second week, there was no significant difference in incidence of headache between groups, and the incidence of headache in the placebo group dropped markedly over time. Conclusion.— Etoricoxib 90 mg taken prior to a 15‐hour ritual fast decreases incidence of and attenuates headache during the first 5 days of the month of Ramadan.