Chisomicines A-C, limonoids from Chisocheton ceramicus

Three new limonoids, chisomicines A-C (1-3), have been isolated from the bark of Chisocheton ceramicus. Their structures were determined by 2D NMR, CD spectroscopic methods, and X-ray analysis. Chisomicine A (1) exhibited NO production inhibitory activity in J774.1 cells stimulated by LPS dose-dependently at high cell viability.     

Iron‐chelating effect of silymarin in patients with β‐thalassemia major: A crossover randomised control trial

This study aimed to determine the potential iron‐chelating effects of silymarin in patients with β‐thalassemia major receiving standard iron‐chelation therapy. We evaluated whether addition of silymarin to standard iron‐chelation therapy could improve iron burden markers and liver and cardiac function in these patients, via a placebo‐controlled, crossover clinical study. Silymarin (140 mg) or placebo were administered thrice daily to all patients (n = 82) for 12 weeks, and after a 2‐week washout period, patients were crossed over to the other groups. Silymarin efficacy was assessed by measuring serum iron level, ferritin level, total iron‐binding capacity and liver and cardiac function on magnetic resonance imaging. Silymarin treatment resulted in a negative change in the serum iron and ferritin levels and a positive change in the total iron‐binding capacity levels (treatment effect, p < .001, p = .06, and p = .05, respectively). Silymarin treatment led to positive changes in cardiac and liver function in both treatment sequences of study; however, this was not statistically significant. There was a negative change in liver iron concentration in both treatment sequences (treatment effect, p = .02). In conclusion, combined iron‐chelation and silymarin therapy was effective for improving the iron‐burden status in patients with β‐thalassemia major.     

The impact of pycnogenol supplementation on plasma lipids in humans: A systematic review and meta‐analysis of clinical trials

The effects of pycnogenol on plasma lipids are controversial. A systematic review and meta‐analysis of clinical trials were conducted to obtain a conclusive result in humans. PubMed, Scopus, and Google Scholar were systematically searched until March 2018, to explore the clinical trials that examined the effect of pycnogenol supplementation on lipid parameters among adult human. Methodological quality of the eligible studies was evaluated using the Cochrane Collaboration's tool. To estimate the effect size, changes in blood lipids were implemented. Results were pooled using a random effects model. Potential sources of heterogeneity were explored by subgroup analysis. A systematic review and meta‐analysis of 14 clinical trials with 1,065 participants suggested a significant increase in plasma concentration of high density lipoprotein cholesterol (HDL‐C; 3.27 mg/dL; 95% CI [0.19, 6.36]; p = 0.038). In contrast, plasma levels of total cholesterol (TC; ?4.45 mg/dL, 95% CI [?11.24, 2.34]; p = 0.199), triacylglycerol (TAG; ?3.64 mg/dL; 95% CI [?17.89, 10.61]; p = 0.616), and low density lipoprotein cholesterol (LDL‐C; ?3.61 mg/dl; 95% CI [?8.76, 1.55]; p = 0.171) were not altered. Adjustment for confounding variables was poor in included studies. Also, these studies did not assess dietary lipid intake. The results indicate that pycnogenol supplementation improves levels of HDL‐C; however, the changes in TC, TAG, and LDL‐C were not clinically relevant. Since there are few phytochemicals that have a significant increasing effect on HDL‐C levels, pycnogenol may have important role in prevention of cardiovascular diseases.     

Wilms tumor gene product: sensitive and contextually specific marker of serous carcinomas of ovarian surface epithelial origin.

Carcinomas of ovarian surface epithelial origin can arise from, and often present at, extraovarian sites. There are few available markers for the positive identification of carcinomas of ovarian surface epithelial origin, which might aid in distinguishing them from metastatic carcinomas, such as of breast, colon, or lung origin. Recently, the Wilms tumor gene product (WT-1) has been shown to be expressed in ovarian surface and mesothelial epithelium. We tested the hypothesis that WT-1 would be a sensitive and specific marker of ovarian surface epithelium carcinomas. An archived series of 116 ovarian carcinomas (57 serous [43 ovarian, 14 extraovarian], 31 mucinous, 15 clear cell, 13 endometrioid), 118 breast carcinomas, 46 colonic carcinomas, and 45 nonsmall cell lung cancers were selected. A polyclonal antibody to the WT-1 gene product was applied to deparaffinized, formalin-fixed tissue sections after epitope retrieval. Fifty-two of 57 (93%) serous carcinomas of ovarian surface epithelial origin were WT-1-positive, in a nuclear pattern, with virtually all the tumor cell population positive in the majority of cases. None of the mucinous, clear cell, or endometrioid ovarian cancers were positive, and only 8 of 118 breast, 0 of 46 colonic, and 0 of 45 lung nonsmall cell carcinomas were WT-1-positive. These findings demonstrate that WT-1 is a highly sensitive and specific marker of serous carcinomas of ovarian surface epithelial origin (both ovarian and extraovarian). These results also contradict recent reports demonstrating WT-1 expression in both breast and lung carcinomas.     

Patho-epidemiology of Cancer Corpus Uteri in Karachi South '1995-1997'.

Aim: To provide demographics and pathology of cancer of the uterine corpus in Karachi. Methodology: Data for 66 incident cases of cancer corpus uteri, ICD-10 category C54-5 registered at the Karachi Cancer Registry, for Karachi South, during a 3 year period, 1st January, 1995 to 31st December 1997 were reviewed. Results: Cancer uterine corpus (1995-97) was the sixth most common malignancy, following breast, oral cavity, ovary, esophagus and cervix. The age standardized incidence rate (ASR) world and crude incidence rate (CIR) per 100,000 were 6.4 (4.73 to 8.01) and 2.9 (2.18 to 3.57). The mean age was 53.7 years (SD 15.6; range 6-90 years). Fifty eight cases were endometrial carcinoma with ASR world and CIR per 100,000 of 5.77 (4.20 to 7.33) and 2.53 (1.88 to 3.18) respectively. Sarcomas comprised 6% of the cases. Approximately a third of the females (28.8%) were below 50 years of age. The age-specific curves showed a gradual increase from the fourth till the seventh decade, followed by an actual apparent decrease in risk after 70 years. Peak incidence was observed in the 65-69 year age group. Presenting symptoms were post-menopausal bleeding (86.4%) and purulent discharge (4%). Associated pathologies included adenomyosis, adenomatous hyperplasia (12% each) or leiomyoma (8%). Associated clinical conditions were diabetes mellitus and hypertension (4% each). The majority of the cases presented as well differentiated (39.4%), localized (59.1%) lesions. Conclusion: The incidence of cancer corpus uteri in Karachi South reflects a moderate risk population, predominantly middle aged with a higher socio-economic status. On the average the malignancy is observed a decade earlier then reported elsewhere. This calls for in-depth investigation of risk factors and identification of underlying etiology.     

Study of cytotoxic and apoptogenic properties of saffron extract in human cancer cell lines

Saffron (dried stigmas of Crocus sativus L.) has been used as a spice, food colorant and medicinal plant for millennia. In this study cytotoxic effect of saffron extract was evaluated in HepG2 and HeLa cell lines. Meanwhile role of apoptosis and ROS were explored. Malignant and non-malignant cells (L929) were cultured in DMEM medium and incubated with different concentrations of ethanolic saffron extract. Cell viability was quantitated by MTT assay. Apoptotic cells were determined using PI staining of DNA fragmentation by flow cytometry (sub-G1 peak). ROS was measured using DCF-DA by flow cytometry analysis. Saffron could decrease cell viability in malignant cells as a concentration and time-dependent manner. The IC50 values against HeLa and HepG2 were determined 800 and 950 μg/ml after 48 h, respectively. Saffron induced a sub-G1 peak in flow cytometry histogram of treated cells compared to control indicating apoptotic cell death is involved in saffron toxicity. This toxicity was also independent of ROS production. It might be concluded that saffron could cause cell death in HeLa and HepG2 cells, in which apoptosis or programmed cell death plays an important role. Saffron could be also considered as a promising chemotherapeutic agent in cancer treatment in future.     

Long-term clinical and pathological effects of cyclosporin in children with nephrosis

The clinical course of eight children with minimal change disease (MCNS) who were treated with cyclosporin (CYA) was retrospectively reviewed (group A). Five children had frequently relapsing (FRNS) and three had steroid-resistant (SRNS) primary nephrotic syndrome (PNS). The mean age (+/-SEM) of the patients at the time of initiation of CYA therapy was 8.01+/-1.30 years. Twelve follow-up renal biopsies, obtained from patients in group A, were compared with baseline 3.36+/-0.76 years after the initiation of CYA. Follow-up renal biopsies from group A were compared with another cohort of eight children with PNS who did not receive CYA (group B, controls). In this later group four children had FRNS and four had SRNS, and all had MCNS on the initial renal biopsy. In group B, the time between the initiation of CYA and the last renal biopsy was 4.07+/-0.82 years. All 36 baseline and follow-up renal biopsies, from group A and B, were retrospectively reviewed by the same pathologist who was blinded to the clinical course and therapy. CYA decreased the number of relapses in patients from group A from 5.20+/-1.02 to 1.14+/-0.63 episodes per year (P<0.05). All patients with SRNS went into remission after initiation of CYA. Estimated creatinine clearance before CYA therapy was unchanged at the end of the observation period, 133+/-10 vs. 131+/-8 ml/min per 1.73m2, respectively. One child developed reversible acute renal failure while on CYA therapy. Attempts to wean three patients off CYA after 3.89+/-0.87 years of CYA therapy were unsuccessful. Mild but increasing tubular atrophy and interstitial fibrosis was observed in serial biopsies of 75% of the patients in group A compared with 25% of the patients in group B, all of whom had MCNS on initial biopsy. In addition, the percentage of renal cortex showing interstitial fibrosis and tubular atrophy in biopsies from group A patients was slightly greater than that of the group B patients (P<0.05). Hence, CYA therapy in children with MCNS is associated with mild renal interstitial fibrosis and tubular atrophy similar to that noted in a minority of the patients with primary MCNS who were not treated with CYA. However, the mild chronic interstitial damage is more frequent and extensive in MCNS patients treated with CYA, suggesting drug-related interstitial alteration. Despite its efficacy and minimal nephrotoxicity in most patients with MCNS, CYA therapy carries the potential for significant morbidity.     

Development of renal hemodynamics: glomerular filtration and renal blood flow.

The regulation of RBF and GFR is essential to understanding renal physiology during mammalian development. Without this knowledge, clinical judgment regarding overall renal function in human neonates, especially those considered high risk, is reduced to guesswork. The plethora of reports in which assessment of RBF and GFR were attempted have provided a legacy purporting the neonatal kidney as immature, inadequate and dysfunctional--nothing could be farther from the truth. Our failure to understand kidney function in the neonate does not justify shifting the blame for unwanted disturbances in fluid and electrolyte balance, metabolic acidosis, and azotemia to a small kidney. After a critical stage of renal development has been reached, subsequent changes in RBF and GFR are only quantitatively different from the adult kidney.