Hala Kfoury

Metformin attenuates streptozotocin-induced diabetic nephropathy in rats through modulation of oxidative stress genes expression

Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion and/or action. One of the most important complications of this metabolic disease is diabetic nephropathy. Hyperglycemia promotes oxidative stress and hence generation of reactive oxygen species (ROS), which is known to play a crucial role in the pathogenesis of diabetic nephropathy. Recent studies have established that metformin, an oral hypoglycemic drug, possesses antioxidant effects. However, whether metformin can protect against diabetic nephropathy has not been reported before. The overall objectives of the present study are to elucidate the potential nephroprotective effect of metformin in a rat diabetic nephropathy model and explore the exact underlying mechanism(s) involved. The effect of metformin on the biochemical changes associated with hyperglycemia induced by streptozotocin was investigated in rat kidney tissues. In addition, energy nucleotides (AMP and ATP), and Acetyl-CoA in the kidney homogenates and mitochondria, and the mRNA expression of oxidative stress and pro-inflammatory mediators were assessed. Our results showed that treatment of normoglycemic rats with metformin caused significant increase in ATP, Acetyl-CoA, and CoA-SH contents in kidney homogenates and mitochondria along with profound decrease in AMP level. On the other hand, treatment of diabetic nephropathy rats with metformin normalized all biochemical changes and the energy status in kidney tissues. At the transcriptional levels, metformin treatment caused significant restoration in diabetic nephropathy-induced oxidative stress mRNA levels, particularly GSTα, NQO1, and CAT genes, whereas inhibited TNF-α and IL-6 pro-inflammatory genes. Our data lend further credence for the contribution of metformin in the nephroprotective effect in addition to its well known hypoglycemic action.

Strategy for second kidney biopsy in patients with lupus nephritis

BACKGROUND Standard clinical and laboratory parameters have limited predictive values for discriminating between active lupus nephritis and chronic disease. The objective of this study was to examine the predictive utility of a second kidney biopsy in patients with lupus nephritis. METHODS Patients with lupus nephritis were advised to have second kidney biopsies at the end of the maintenance phase of their therapies. Baseline and second renal biopsies were re-classified by pathologists blinded to the clinical data. The relationships between remission status and histological parameters were examined. RESULTS Included in this study were 77 patients followed up for a median duration of 8.7 years (interquartile range, 5.3-10.1 years). Their renal survival rates were 93% for those in complete remission (CR), 69% for partial remission (PR) and 41% for no remission (NR). One-third of the patients with PR and 14% of patients with NR had no histological evidence of active disease on second biopsy. At the second biopsy, but not at the baseline biopsy, activity index was predictive of survival. The 10-year renal survival rate was 100% for those with an activity index of 0, 80% for those with an activity index of 1 or 2 on the second biopsy and 44% for those with an index of >2, regardless of remission status. CONCLUSION Second kidney biopsy at the end of maintenance phase of therapy is an important diagnostic and prognostic tool that could guide physicians to safer practices with better outcomes.

Genome scan study of prostate cancer in Arabs: identification of three genomic regions with multiple prostate cancer susceptibility loci in Tunisians.

BackgroundLarge databases focused on genetic susceptibility to prostate cancer have been accumulated from population studies of different ancestries, including Europeans and African-Americans. Arab populations, however, have been only rarely studied.MethodsUsing Affymetrix Genome-Wide Human SNP Array 6, we conducted a genome-wide association study (GWAS) in which 534,781 single nucleotide polymorphisms (SNPs) were genotyped in 221 Tunisians (90 prostate cancer patients and 131 age-matched healthy controls). TaqMan® SNP Genotyping Assays on 11 prostate cancer associated SNPs were performed in a distinct cohort of 337 individuals from Arab ancestry living in Qatar and Saudi Arabia (155 prostate cancer patients and 182 age-matched controls). In-silico expression quantitative trait locus (eQTL) analysis along with mRNA quantification of nearby genes was performed to identify loci potentially cis-regulated by the identified SNPs.ResultsThree chromosomal regions, encompassing 14 SNPs, are significantly associated with prostate cancer risk in the Tunisian population (P = 1 × 10-4 to P = 1 × 10-5). In addition to SNPs located on chromosome 17q21, previously found associated with prostate cancer in Western populations, two novel chromosomal regions are revealed on chromosome 9p24 and 22q13. eQTL analysis and mRNA quantification indicate that the prostate cancer associated SNPs of chromosome 17 could enhance the expression of STAT5B gene.ConclusionOur findings, identifying novel GWAS prostate cancer susceptibility loci, indicate that prostate cancer genetic risk factors could be ethnic specific.

Dorsal dimelia of a thumb

Dorsal dimelia (congenital palmar polyonychia) of the hand is defined as the presence of an ectopic palmar nail at the tip of the finger with evidence of dorsalisation of the palmar skin. All reported human cases involved the little or ring fingers and none of the affected digits were subjected to detailed examination. We report the first human case of dorsal dimelia involving a thumb, and provide gross and histological examination of the affected digit. We also review the embryology of this rare deformity and previously reported cases.

The Histological Spectrum of Early Mycosis Fungoides: A Study of 58 Saudi Arab patients.

OBJECTIVES The histopathological diagnosis of Mycosis Fungoides (MF) is challenging in its early stages and can easily be confused with inflammatory dermatoses. This study aims to; (i) assess the frequency and significance of different histopathological parameters in early MF, seen in Saudi patients, and (ii) to study the utility of these parameters in differentiating between early MF and inflammatory dermatoses. METHODS This is a five years study of 66 skin biopsies generated from 58 patients with clinically suspicious MF lesions or early patch stage MF. These cases were retrieved from the archives of the Department of Pathology, King Khalid University Hospital, Riyadh from the year 2002 to 2006. Histological criteria were assessed and graded semi-quantitatively on a four-point scale by a dermatopathologist and two pathologists independently. RESULTS The histological parameters suggesting the diagnosis in early stages MF include epidermotropism, dermal fibrosis, Pautriers micro abscesses, Basal alignment of neoplastic lymphocytes, hyperconvoluted dermal and epidermal lymphocytes and grandiosity sign (size of lymphocytes becoming larger as they migrate towards granular layer of epidermis). These parameters on univariate analysis achieved statistical significance (p<0.05) in differentiating MF from non-MF cases. In addition, hyperconvoluted dermal and epidermal lymphocytes proved to be highly reliable with high specificity and sensitivity. CONCLUSION The histopathological diagnosis of early MF lesions and their discrimination from inflammatory simulators can be achieved by carefully observing the hyperconvoluted dermal and epidermal lymphocytes along with the constellation of the other parameters.

A Delayed Allergic Reaction to Polypropylene Suture Used in Flexor Tendon Repair: Case Report

We report a patient who developed a delayed hypersensitivity reaction to a polypropylene suture used in flexor pollicis longus repair. We also review the literature and aim to increase the awareness of hand surgeons to the presentation, diagnosis, and management of these rare cases.

Cytomegalovirus disease in a renal transplant recipient: the importance of pre-transplant screening of the donor and recipient

A 16-year-old female patient who was born with a single kidney developed chronic kidney disease during her early childhood due to reflux nephropathy and recurrent urinary tract infection. She progressed to end-stage renal disease (ESRD) and was commenced on renal replacement therapy in the form of peritoneal dialysis in May 2011. Subsequently, she underwent living unrelated donor kidney transplantation in China. She was hospitalized soon after returning to Saudi Arabia for management of high-grade fever, shortness of breath, and deterioration of renal function, which was found to be due to cytomegalovirus (CMV) disease, proved by kidney biopsy and presence of high level of anti-CMV immunoglobulins. Allograft biopsy showed mature viral particles sized between 120 and 149 nm in the nuclei of the glomerular endothelial cells. The patient was treated with valgancyclovir and specific CMV immunoglobulin, as well as by reducing and even stopping the dose of tacrolimus and mycophenolate. Despite all these measures, her condition continued to deteriorate and she finally died. Our study emphasizes that unrelated renal transplantation, especially if unplanned and improperly prepared, is a very risky procedure that might transfer dangerous diseases and increase the morbidity and mortality of the patients. We strongly stress the need for mandatory and proper screening for CMV carrier status among donors as well as recipients prior to transplantation. Also, a recommendation is made to reject CMV-positive donors.

Mimicry of Minute Pulmonary Meningothelial-like Nodules to Metastatic Deposits in a Patient with Infiltrating Lobular Carcinoma: A Case Report and Review of the Literature

Minute pulmonary meningothelial-like nodules (MPMNs) are incidentally found lesions in lung resection specimens and autopsies. MPMNs have been associated with neoplastic and non-neoplastic pulmonary conditions and occasionally with extrapulmonary diseases. We report a case of a female patient presenting with invasive lobular carcinoma of the breast and MPMNs, masquerading as metastatic deposits. We describe the morphological, immunohistochemical and ultrastructural features of MPMNs and emphasize the importance of their recognition for proper staging and treatment of patients. To our knowledge, this is the first case in the English literature describing this coexistence.

Toxicity evaluation of methoxy poly(ethylene oxide)-block-poly(ε-caprolactone) polymeric micelles following multiple oral and intraperitoneal administration to rats

Methoxy poly(ethylene oxide)-block-poly(ɛ-caprolactone) (PEO-b-PCL) copolymers are amphiphilic and biodegradable copolymers designed to deliver a variety of drugs and diagnostic agents. The aim of this study was to synthesize PEO-b-PCL block copolymers and assess the toxic effects of drug-free PEO-b-PCL micelles after multiple-dose administrations via oral or intraperitoneal (ip) administration in rats. Assembly of block copolymers was achieved by co-solvent evaporation method. To investigate the toxicity profile of PEO-b-PCL micelles, sixty animals were divided into two major groups: The first group received PEO-b-PCL micelles (100 mg/kg) by oral gavage daily for seven days, while the other group received the same dose of micelles by ip injections daily for seven days. Twenty-four hours following the last dose, half of the animals from each group were sacrificed and blood and organs (lung, liver, kidneys, heart and spleen) were collected. Remaining animals were observed for further 14 days and was sacrificed at the end of the third week, and blood and organs were collected. None of the polymeric micelles administered caused any significant effects on relative organ weight, animal body weight, leucocytes count, % lymphocytes, liver and kidney toxicity markers and organs histology. Although the dose of copolymers used in this study is much higher than those used for drug delivery, it did not cause any significant toxic effects in rats. Histological examination of all the organs confirmed the nontoxic nature of the micelles.

Tubulo-reticular inclusions in lupus nephritis: Are they relevant?

Tubulo-reticular inclusions (TRIs) are organized subcellular structures that may be found in endothelial cells of patients with systemic lupus erythematosus (SLE). This study was conducted to determine the presence or absence of TRIs and their correlation with the activity index (AI) and lupus nephritis (LN) class. A retrospective analysis of 57 cases of LN over a three-year period (2008-2011) was performed from medical records of the King Khalid University Hospital (KKUH), Riyadh. After reviewing and sorting them by class as per the International Society of Nephrology (ISN/RPS) 2004 classification of LN, the cases were divided according to the presence or absence of TRIs. The relationships between the presence or absence of TRIs and the AI were determined. Of the 57 kidney biopsies reviewed, 49 were proliferative cases (Class III and IV), of which 12 (24.5%) had TRIs. The mean AI was 6.01 ± 3.8 and the mean chronic index was 3.0 ± 1.5. Four (11.4%) class IV cases had a high AI, while no Class III cases with TRIs showed increased activity. The presence of TRIs was significantly associated with the AI (r = 9.40, P = 0.002), but not with LN class (r = 0.099, P = 0.753). Examining for TRIs in LN is still favorable and helpful in cases where the diagnosis of SLE is pending or not yet established, although the presence of TRIs is not a specific finding.