Oxidative renal damage in pyelonephritic rats is ameliorated by montelukast, a selective leukotriene CysLT1 receptor antagonist

Urinary tract infections may induce severe inflammation, transient impairment in renal function and scar formation, ranging in severity from acute symptomatic pyelonephritis to chronic pyelonephritis, which have a potential to lead to renal failure and death. The present study aimed to investigate the possible protective effect of montelukast, a selective antagonist of cysteinyl leukotriene receptor 1 (leukotriene CysLT1), against Escherichia coli-induced oxidative injury and scarring in renal tissue. Wistar rats were injected 0.1 ml of E. coli (ATCC 25922 10(10) cfu/ml) or saline into left renal medullae. Six rats were assigned as the sham group and were given 0.1 ml 0.9% NaCl. Pyelonephritic rats were treated with either saline or montelukast immediately after surgery and at daily intervals. Twenty-four hours or one week after E. coli injection, rats were decapitated and the kidney samples were taken for histological examination or determination of renal malondialdehyde, glutathione (GSH) levels, myeloperoxidase (MPO) activity, and collagen contents. Formation of reactive oxygen species in renal tissue samples was monitored by using chemiluminescence technique with luminol and lucigenin probes. Creatinine, blood urea nitrogen and lactate dehydrogenase (LDH) activity were measured in the serum samples. E. coli inoculation caused significant increases in malondialdehyde level, MPO activity, chemiluminescence levels and collagen content, while GSH level was decreased in the renal tissues (p<0.05-0.001). On the other hand, serum TNF-alpha, LDH, blood urea nitrogen and serum creatinine levels were elevated in the pyelonephritic rats as compared to control group. Leukotriene CysLT1 receptor antagonist montelukast reversed all these biochemical indices, as well as histopathological alterations, that were induced by acute pyelonephritis. It seems likely that montelukast protects kidney tissue by inhibiting neutrophil infiltration, balancing oxidant-antioxidant status, and regulating the generation of inflammatory mediators suggesting a future role for leukotriene CysLT1 receptor antagonists in the treatment of pyelonephritis.     

Horizontal muscle transposition or oblique muscle weakening for the correction of V pattern?

Purpose

To report and to analyze the efficacy of horizontal rectus muscle transposition and inferior oblique muscle weakening in terms of pattern correction for patients with V pattern.

Methods

The review of the medical files identified 55 patients who had esotropia (ET) or exotropia (XT) with V pattern. The primary outcome measure was the amount of V pattern collapse (Δ).

Results

Of the 55 patients (mean age 22.1±9.5 years), 27 (49.1%) were males and 28 (50.9%) were females. The type of deviations was XT in 30 patients (54.5%) and ET in 25 patients (45.5%). Inferior oblique muscle weakening was performed in 43 (78.2%) patients, whereas horizontal muscle transposition was carried out in 12 (21.8%) patients in addition to recession-resection procedures. The amount of pattern was significantly reduced in both groups (P=0.01 for the horizontal offset group and P<0.01 for the oblique muscle weakening group).

Conclusion

Oblique muscle weakening surgery and horizontal muscle offset are effective in the correction of V pattern when the amount of pattern is under 30Δ.     

Clinical outcomes in patients who received lapatinib plus capecitabine combination therapy for HER2-positive breast cancer with brain metastasis and a comparison of survival with those who received trastuzumab-based therapy: a study by the Anatolian Society of Medical Oncology

Purpose

In this study, we investigated the effect of lapatinib plus capecitabine treatment in HER2-positive breast cancer patients with brain metastasis.

Methods

Of 405 metastatic breast cancer patients with brain metastases at referral centers in Turkey, 46 were treated with lapatinib plus capecitabine only after the development of brain metastasis. Patients who only received trastuzumab-based therapy after the development of brain metastases were accepted as the historic control group for survival analyses (n = 65). Patients who received both drugs consecutively or sequentially were excluded from the analyses (n = 34).

Results

Median age among 46 patients who received lapatinib plus capecitabine therapy was 45 years (27–76), and median time for development of brain metastases was 11.9 months (0–69 months). Twenty-six out of 38 patients who received lapatinib plus capecitabine and had extracranial metastasis showed partial response or stable diseases (68.4 %). Grade 3-4 toxicity was observed in eight patients (17.3 %). Median overall survival (OS) in patients treated with lapatinib plus capecitabine was significantly increased compared to that in patients treated with trastuzumab-based therapy (19.1 vs. 12 months, respectively, p = 0.039). The incidence of cerebral death was slightly decreased in patients who received lapatinib plus capecitabine compared to those who received trastuzumab-based therapy (32 vs. 43.4 %, p = 0.332). In the multivariate analysis, lapatinib plus capecitabine therapy remained an independent positive predictor for survival [odds ratio (OR), 0.57; p = 0.02].

Discussion

Although this retrospective multicenter study had several limitations, the results suggest that undergoing lapatinib plus capecitabine therapy after the diagnosis of brain metastasis may further improve survival compared to undergoing only trastuzumab-based therapy.     

Antimycobacterial Activity of Taxus baccata

Crude extracts prepared from various parts of Taxus baccata L. have been evaluated for their antimycobacterial activity. A CHCl₃ fraction of the heartwood and ethanol extract of the leaves exhibited a minimum inhibitory concentration value (MIC) against Mycobacterium tuberculosis H₃₇Ra strain of 200?µg/ml.     

Electrical activity in pancreatic islet cells: The VRAC hypothesis

A major aspect of stimulation of β-cell function by glucose is the induction of electrical activity. The ionic events that underlie β-cell electrical activity are understood in some detail. At sub-stimulatory glucose concentrations, the β-cell is electrically 'silent'. Increasing the glucose concentration to stimulatory levels results in a gradual depolarisation of the membrane potential to a threshold potential where 'spikes' or action potentials are generated. These action potentials represent the gating of voltage-sensitive Ca2(+) channels, leading to Ca2(+) entry into the cell, thus triggering the release of insulin. The stimulatory actions of glucose on the β-cell depend on the metabolism of the hexose. A major question concerns the molecular mechanism(s) whereby β-cell plasma membrane potential is regulated by changes in glucose metabolism in the cell. This article provides a brief summary of the evidence suggesting that, in addition to metabolically-regulated K(ATP) channels, β-cells are equipped with a volume-regulated anion channel that is activated by glucose concentrations within the range effective in modulating electrical activity and insulin release.     

A case of textile dermatitis due to disperse blue on the surgical wound

Disperse blue (DB) 106 and DB 124 are the most frequent fabric dye allergens inducing textile dermatitis, but contact allergy to them may easily undiagnosed because the clinical picture usually needs high index of suspicion. We present the case of a 35-year-old woman who was referred for a recurred lesion over the incision scar of right total hip replacement surgery, which did not respond to treatment with povidone-iodine, mupirocin, and rifampicin. Patch testing, conducted with a European standard series and therapeutics that were used in the treatment of the lesion, revealed a positive reaction to dispersion mix blue 106/124. The patient was questioned in detail and reported that she has been wearing dark-colored synthetic panties for long years. The correlation was done between the positive antigen in the patch test and the clinical findings. The patient was treated with a corticosteroid cream for 2 weeks. She did not wear any dark-colored synthetic panties afterward and no flare-up was seen in the follow-up period. In this report, we emphasize the importance of detailed questioning of patients and that contact dermatitis should be considered potential cause of dermatitis at skin sites where the barrier function is compromised.     

Biochemical and histologic study of lethal cisplatin nephrotoxicity prevention by mirtazapine

BackgroundCisplatin is a platinum derivative frequently used in the chemotherapy of different solid tumors. This biochemical and histologic study investigated a possible protective effect of mirtazapine with regard to cisplatin-induced nephrotoxicity in the rat.MethodsThe animals were divided into 4 groups: 15 mg/kg mirtazapine + 10 mg/kg cisplatin, 30 mg/kg mirtazapine + 10 mg/kg cisplatin, only 10 mg/kg cisplatin and negative control (healthy) group. During 14 days, the treatment and treated control group took drugs, while the healthy animals were given distilled water on the same schedule. All animals were sacrificed by high-dose anesthesia at the end of the 14 days of treatment; their kidneys were removed and subjected to histologic and biochemical study.ResultsIn both of the doses we used, mirtazapine decreased the levels of malondialdehyde, creatinine, blood urea nitrogen and myeloperoxidase activity when compared to cisplatin group. On the other hand, it increased total glutathione level in all doses. Slight histopathological findings were determined in mirtazapine groups when compared to cisplatin control group.ConclusionIn the light of our results and literature knowledge, we can conclude that the protective effect of mirtazapine in cisplatin toxicity originates from its own antioxidant activity.     

Colorimetric-plate method for rapid disk diffusion susceptibility testing of Escherichia coli

Here, we report a laboratory-developed colorimetric-plate method for rapid disk diffusion susceptibility testing of Escherichia coli. One hundred isolates were evaluated. Categorical agreement between the colorimetric plate and the standard disk diffusion method was 99%. Mean time to results was 7.07 h (95% confidence interval, 5.96 to 8.19).