Comparative study on the therapeutic effects of bone marrow mesenchymal stem cells versus platelet rich plasma on the pancreas of adult male albino rats with streptozotocin-induced type 1 diabetes mellitus.

BACKGROUND: The optimal treatment for autoimmune type 1 diabetes mellitus (T1DM) is endogenous regeneration of the pancreatic beta-cell. This can be achieved either by transplanting bone marrow mesenchymal stem cells (BMSCs) or injecting platelet-rich plasma (PRP). Current research reviewed a T1DM model and compared the effect of BMSCs on exocrine and endocrine pancreas portions versus PRP. MATERIALS AND METHODS: Rats were divided into four groups: Control group, Diabetic group (single streptozotocin dose 60 mg/kg IP), Diabetic + PRP group (PRP, 0.5 mL/kg SC twice weekly/4 weeks given to diabetic rats) and Diabetic + BMSCs group (1 mL of PKH26 labelled MSCs suspension in buffer phosphate solution, 3 × 106 cells/mL IV to diabetic rats). Glucose, amylase and lipase levels were calculated and pancreases were designed for light, electron microscopic, immunohistochemistry, morphometry and statistical analysis. RESULTS: Diabetic rats exhibited elevated glucose, decreased amylase and lipase compared to control rats. In addition, variable histological degenerative changes in the form of congested blood vessels have been identified with a significant increase in the mean area percentage of collagen, a significant decrease in the diameter of the islets, the number of cells in the islets of Langerhans and the number of zymogen granules. Ultrastructural findings exhibited distorted Golgi apparatus morphology, degenerated mitochondria, pyknotic nuclei, and few secretory beta-cell granules. CONCLUSIONS: Administration of BMSCs to diabetic group significantly increased the number of cells and diameter of Langerhans islets and the number of zymogen granules compared to Diabetic group as well as Diabetic + PRP group. BMSCs could be considered more efficient than PRP in the treatment of type 1 diabetes.

Effect of nicotine on spermatogenesis in adult albino rats.

This study aimed to assess the effects of nicotine on spermatogenesis in 140 mature male albino rats divided into group A (controls), group B (sham controls), group C (nicotine treated) and group D (nicotine withdrawal). Group C was subdivided into CI, CII, CIII according to the dose of injected nicotine (0.2, 0.4 and 0.6 mg nicotine per 100 g per day), where each subgroup was further subdivided according to the treatment duration into subgroups a, b and c that received nicotine for 2, 4 and 8 weeks. Group D received nicotine for 8 weeks followed by withdrawal for another 8 weeks to assess testicular recovery. Testicular tissue sections were subjected to haematoxylin and eosin, Masson's trichrome stains and morphometry. The results showed that nicotine caused degenerative changes in the seminiferous tubules, revealed by altered general tubular architecture, decreased thickness of the spermatogenic cell masses, Sertoli cell vacuolation and thickened basal lamina. These changes were proportional to the nicotine dose and duration. Following nicotine withdrawal, regeneration of the damaged seminiferous tubules was observed to be rather complete in CI group. It is concluded that nicotine could adversely affect testicular spermatogenesis in a dose- and time-dependent manner which would be almost reversible after nicotine withdrawal, especially after small doses.

Adverse effects of energy drink on rat pancreas and the therapeutic role of each of bone marrow mesenchymal stem cells and Nigella Sativa oil.

BACKGROUND: Energy drinks have been observed to threaten public health leading to many medical problems. Bone marrow-derived mesenchymal stem cells (BMSCs) have broad prospects in tissue regeneration. Nigella Sativa (NS) possess great therapeutic properties for the treatment of a wide range of diseases. MATERIALS AND METHODS: Forty adult male albino rats were divided into: control group and treated group. The treated group was further subdivided into: energy drink subgroup 2a, BMSCs-injected subgroup 2b, NS-injected subgroup 2c. Histological, immunohistochemical and biochemical assessment was performed. RESULTS: Administration of energy drink revealed that it adversely affected the pancreatic cytoarchitecture. BMSCs and NS have been similarly observed to significantly ameliorate the histological, biochemical and immunohistochemical changes induced by energy drink. CONCLUSIONS: The extent of pancreatic regeneration, exerted by each of BMSCs and NS oil, is nearly similar but the effect of BMSCs is more superior; however, NS could be privileged to BMSCs as a line of treatment being easily accessible and of lower cost.

Interleukin-1beta, transforming growth factor-beta1, and bradykinin attenuate cyclic AMP production by human pulmonary artery smooth muscle cells in response to prostacyclin analogues and prostaglandin E2 by cyclooxygenase-2 induction and downregulation of adenylyl cyclase isoforms 1, 2, and 4.

Increased levels of inflammatory cytokines contribute to the pathophysiology of pulmonary hypertension. Prostacyclin (PGI2) analogues, which relax pulmonary vessels mainly through cAMP elevation, have a major therapeutic role. In this study, we show that prolonged incubation with bradykinin (BK), interleukin-1beta (IL-1beta), and transforming growth factor-beta1 (TGF-beta1) markedly impairs cAMP accumulation in human pulmonary artery smooth muscle cells in response to short-term incubation with prostaglandin E2 (PGE2) and the PGI2 analogues iloprost and carbaprostacyclin. A similar reduction in cAMP accumulation in response to a direct adenylyl cyclase activator, forskolin, suggested that the effect was attributable to downregulation of adenylyl cyclase. Reverse transcriptase-polymerase chain reaction studies showed downregulation of adenylyl cyclase isoforms 1, 2, and 4. The effect of IL-1beta, BK, and TGF-beta1 on cAMP levels was abrogated by the selective COX-2 inhibitor NS398. Furthermore, it was mimicked by prolonged incubation with the COX-2 product PGE2 and PGI2 analogues or the COX substrate arachidonic acid, suggesting that it was mediated by endogenous prostanoids produced by COX-2. Consistent with this, IL-1beta, BK, and TGF-beta1 all induced COX-2 and PGE2 release. These results show that BK, IL-1beta, and TGF-beta1 downregulate adenylyl cyclase in human pulmonary artery smooth muscle cells via COX-2 induction and prostanoid release. This suggests a novel mechanism whereby mediators and cytokines produced in pulmonary hypertension may impair the therapeutic effects of prostacyclin analogues such as iloprost and carbaprostacyclin.

Five year follow up of biocolonisable microporous fluorocarbon haptic (BIOKOP) keratoprosthesis implantation in patients with high risk of corneal graft failure.

AIM: To study the anatomical and visual performance following implantation of a model of artificial cornea and to evaluate the postoperative long term complications. METHODS: 11 eyes of 11 patients with bilateral corneal blindness considered as potentially having high risk of failure of penetrating corneal keratoplasty were implanted with biocolonisable Kpro keratoprosthesis (BIOKOP I, FCI, Rantigny, France) in the period between January 1996 and May 1998. Only one eye was implanted in all patients and followed up for a period of 60 months. The visual outcome, anatomical and functional stability, complications, and the general performance of the keratoprosthesis were evaluated. RESULTS: The keratoprosthesis (BIOKOP I) only 36.3% remained in position to date. In the patients' last visit five eyes (45.4%) were blind and one (9.0%) showed a slight improvement in the best corrected visual acuity (BCVA) in comparison to preoperative tests. Six eyes (54.5%) showed improved BCVA before having postoperative complications. Four eyes underwent replacement of a BIOKOP I Kpro with a BIOKOP II as a result of extrusion. The keratoprostheses remained anatomically in situ for a mean of 25.5 months and their functional performance period was limited to a mean of 22 months. CONCLUSION: Corneal keratoprosthesis (BIOKOP I, II) does not provide a stable anatomical relation with the surrounding ocular structures. Its ability to restore vision is limited to a short postoperative period in eyes implanted with severe ocular surface disease.

Prevalence and associated risk factors of male erectile dysfunction among patients on hemodialysis and kidney transplant recipients: a cross-sectional survey from Sudan.

Male erectile dysfunction (ED) is an important issue worldwide occurring in 5-69% of men in community-based studies. It is more common in patients with chronic kidney disease (CKD) and those on peritoneal as well as hemodialysis (HD), occurring in more than 80% of patients. In Sudan, there is no previous report on ED among patients with CKD. A cross-sectional study was done to determine the prevalence of ED and its associated risk factors among Sudanese CKD patients on HD and those who underwent renal transplant. This was conducted in Khartoum, Sudan from October 2005 to July 2006 including all married men who were on maintenance HD for more than three months and all married men who had received renal transplantation at least three months earlier. Single, divorced/separated men, those whose wives were living away, those who were bed-bound and those with cognitive impairment were also excluded. After obtaining consent for participation, demographic and clinical data were collected by using anonymous questionnaires and the Arabic version of International Index of Erectile Function (IIEF; the Egyptian version). Patients who did not participate in full and proper manner were considered as "non-responders." A total of 146 patients, 106 HD patients, and 40 renal transplant recipients completed the IIEF questionnaire. Non-responders constituted 43.7% and 54.5% of HD and transplant recipient patients, respectively. Blood samples were taken after completion of the IIEF questionnaire to determine the required investigations. ED prevalence was high among our study patients, 83% among the HD patients and 67.5% among the renal transplant recipients. Univariate analysis showed that there was a trend, although non-significant, of older age being associated with ED in both groups. Similar association was seen in those who were under-dialyzed in the HD group and DM in the transplant recipient group. Previous history of ED was significantly associated with current presence of ED in both groups. More studies with larger sample size are needed to clarify the results of this study.

IL-1beta, BK, and TGF-beta1 attenuate PGI2-mediated cAMP formation in human pulmonary artery smooth muscle cells by multiple mechanisms involving p38 MAP kinase and PKA.

We have previously shown that interleukin (IL)-1beta, transforming growth factor (TGF)-beta1, or bradykinin (BK) impair cAMP generation in response to prostacyclin analogs in human pulmonary artery smooth muscle (PASM), suggesting that inflammation can impair the effects of prostacyclin analogs on PASM in pulmonary hypertension. Here we explored the biochemical mechanisms involved. We found that IL-1beta, BK, and TGF-beta1 reduced adenylyl cyclase isoform 1, 2, and 4 mRNA, increased Galphai protein levels, and reduced prostacyclin receptor (IP receptor) mRNA expression. In contrast, Galphas protein levels were unchanged. Protein kinase A (PKA) (H-89, KT-2750, PKIm) and p38 mitogen-activated protein (MAP) kinase (SB-202190) inhibitors attenuated these effects, but protein kinase C (bisindolylmaleide) or phosphoinositol 3-kinase (LY-294002) inhibitors did not. Fluorescent kemptide assay and Western blotting confirmed that PKA and p38 MAP kinase were activated by IL-1beta, BK, and TGF-beta1. These studies suggest that IL-1beta, BK, and TGF-beta1 impair IP receptor-mediated cAMP accumulation by multiple effects on different components of the signaling pathway and that these effects are PKA and p38 MAP kinase dependent.