Study of the Effect of Route of Administration of Mesenchymal Stem Cells on Cisplatin-Induced Acute Kidney Injury in Sprague Dawley Rats

BACKGROUND AND OBJECTIVES: Mesenchymal stem cells (MSCs) have been shown to ameliorate cisplatin-induced acute kidney injury (AKI). The present study compares the efficacy of different routes of MSCs administration on kidney damage and regeneration after cisplatin-induced AKI. METHODS: A single intraperitoneal injection of cisplatin (5 mg/kg) was used to induce AKI in 160 rats. MSCs (5×106) were given by either intravenous, intra-arterial or kidney sub capsular injection one day after cisplatin injection. Suitable control groups were included. Rats were sacrificed at 4, 7, 11 and 30 days after cisplatin injection. Kidney function parameters, kidney tissue oxidative stress markers, and scoring for renal tissue injury, regeneration and chronicity were all determined. RESULTS: MSCs by any routes were able to ameliorate kidney function deterioration and renal tissue damage induced by cisplatin. The overall results of the three routes were equal. Differences between the different routes in one parameter were transient and inconsistent with other parameters. CONCLUSION: Changing the route of MSCs injection does not have a major influence on the outcome. Future evaluation should focus on differences between the routes of administration considering the long term safety.

Prescribing rationality in Khartoum state, Sudan: an update

Rational prescribing is one of the essential components of good medical practice targeted to provide successful and relatively safe drug therapies. The present study was carried to assess the rationality of the current prescribing practices in Khartoum State. A descriptive, observational, 1-time study was carried out in Khartoum State hospitals and community pharmacies, to evaluate the five main prescribing indicators adopted by the WHO. Data were collected using the WHO prescribing indicator form. The total number of prescriptions collected and analyzed was 7377 prescriptions, 67% from Khartoum city, 22.5% from Khartoum North city and 10.5% from Omdurman city. The total number of drugs prescribed was 20,482, the average number of drugs per prescription: 2.776 drugs, percentage of generics: 37.3%, percentage of antibiotics: 54.3%, percentage of injections: 38.6% and the percentage of drugs on the essential drug list [EDL] was 72.8%. The number of encounters included in this study is sufficiently large compared to other previously reported studies allowing us to consider the results obtained as an acceptable representative of the total population to describe the overall prescribing pattern. Except for the value obtained for the percentage drugs on the EDL, the values of the other four indicators are indicative of prescribing irrationality in the study population. The observed irrational prescribing behavior necessitates the development of certain policies as well as practical and effective implementation mechanisms to promote rational prescribing. We, therefore, recommend the conduction of one or more of three interventions namely, administrative, managerial and/or educational addressing the prescribers population

Effects of circadian blood pressure variability on aortic distensibility in untreated and treated hypertensive individuals

Background: Blood Pressure [BP] exhibits a circadian periodic variation with lower values during the night and higher values during the day. Blunted BP decline during nighttime, which is called non-dipping pattern, in hypertension [HTN], is associated with higher cardiovascular [CV] morbidity and mortality, however, this association has not gone undisputed. Furthermore, the influences of non-dipper BP on aortic elastic properties have not yet been widely studied

Objectives: the aim was to evaluate the effect of circadian BP changes [dipping and non-dipping state] on aortic dispensability in untreated and treated hypertensive subjects using standard Doppler echocardiography

Patients and Methods: this study included 87 out of 180 subjects classified according to their BP profile and clinical status into 3 groups. Group [1]: 28 patients with untreated HTN, Group [2]: 34 patients with treated HTN, and Group [3]: 25 normal controls. Each group was further classified into 2 subgroups: [a: dippers and b: non-dippers]. We excluded every patient with any systemic disease or CV risk factor that may affect aortic structural and/or functional characteristics apart from HTN. All study populations were subjected to thorough history taking, clinical examination, laboratory work up, ECG, 24h ABPM, standard echo Doppler

Results: the study included 44 [51%] males and 43 [49%] females; their mean age was 42 +/- 8, and ranging between 29-55 years. In untreated hypertensives, systolic and diastolic aortic diameters [SAD, DAD] [aortic anatomical parameters] were similar in both dippers and non dippers, while functional parameters [aortic strain distensibility and stiffness index] [AS, AD, and ASI] showed only trends for more impairment in non dippers than dippers, however, these did not reach statistical significance. In treated hypertensives, also aortic anatomical parameters were similar in both dippers and non dippers, while aortic functional parameters were significantly more impaired in non-dippers than in both dippers and controls. We also found that both aortic anatomical and functional parameters and so elastic properties showed significant correlations mainly with systolic load in untreated hypertensives, while correlated mainly with nighttime ABP measurements in treated hypertensives

Conclusion: this study confirmed that, in untreated hypertensive, aortic distensibility was slightly more impaired in non-dippers compared to dipper ones, but this difference did not reach statistical significance and it correlated positively mainly with systolic load. While in treated hypertensives, AD was significantly more impaired in non-dippers compared to dippers and it correlated positively mainly with nighttime measurements

possible cytoprotective role of L-arginine and misoprostol in some radiocontrast media induced toxicity

Despite recent medical progress in supportive medical therapy, the frequency of hospital aquired acute renal failure has increased in recent years.Of the multiple etiologies which can cause such renal impairment, radiocontrast media are recorded to be the third common cause of hospital aquired acute renal failure.In attempts to minimize the radiocontrast induced nephrotoxicity, L-arginine and misoprostol were used as cytoprotective agents against such toxicity. This study was conducted on 180 adult male albino rats. They were classified into: negative control group I distilled water group II, gum acacia group III, L-arginine group IV, misoprostol groupV, diatrizoate group VI, iopromide group VII, L-arginine and diatrizoate group VIII, misoprostol and diatrizoate group IX, L-arginine and iopromide group X, misoprostol and i opromid group Xl, gentamicin group XII, gentamicin and diatnzoate group XIII, gentamicin and iopromide grou XIV, gentamicin, L-arginine and diatrizoate group XV, gentamicin, misoprostol and diatrizoate group XVl, gentamicin, L-arginine and iopromide group XVll. The last group was gentamicin, misoprostol and iopromide group XVIII. At the end of the experimental period the animals were sacrificed, BUN and serum creatinine and urinary beta2 microglobulin and gamma glutamyl transpeptidase [GGT] analyses as well as histopathological examination of the kidney sections were carried out. The results revealed that in groups VI and VII there was significant increase in BUN, serum creatinine, urinary beta2 microglobulin and GGT with degeneradive changes in the proximal convoluted tubules in comparison with group I. These changes were more observed in group VI than in group VII.While in group XIII, there was marked increase in BUN and serum creatinine with aggravation in the renal histopathological changes in comparison with group XII. Moreover misoprostol appeared more effective than L-arginine in nephroprotection when it was given five days before the radiocontrast media either in groups with health kidney [VIII, IX, X and XI] or groups with compromized kidney [XV, XVI, XVII and XIII]

Analysis of markers of cytotoxicitty and apoptosis in HCV

To determine the role of CD8+ T-cell responses and apoptosis in mediating liver injury in chronic hepatitis C, an analysis of cytotoxic CD8+ T-cell and apoptosis markers was performed in 70 patients with proven chronic hepatitis C and 30 controls. CD8+ T-cell responses to a panel of HCV proteins and peptides were performed in an Elispot assay. Apoptosis was detected by peripheral expression of Fas, Fas ligand and perforin as well as apoptosis of hepatocytes was also detected using transferase-mediated immunohistochemical d-UTP biotin nick labeling [TUNEL] and flowcytometry. Cytotoxic HLA A2 restricted responses were detected in 54 patients. The expression of Fas antigen, Fas ligand and perforin was significantly increased in patients compared with the control subjects. Immunohistochemical intracytoplasmic Fas expression and the apoptosis index of hepatocytes directly correlated to the necroinflammatory activity in the liver. A direct significant correlation was detected between the CD8+ T-cell responses and the apoptosis index. These results indicated that HCV- specific CD8+ T-cell responses and apoptosis can be detected in the majority of patients with chronic HCV and liver injury in chronic HCV is mediated through these responses

Detection of intrapulmonary vascular dilatations [IPVD] in patients with chronic liver disease by contrast-enhanced echocardiography using indocyanine green dye VS. isotonic saline

Intrapulmonary vascular dilatations [IPVD] are extrahepatic complications of acute and chronic liver disorders that can result in severe hypoxemia. Contrast-enhanced [CE] echocardiography provides a noninvasive method to detect right-to- left shunting associated with IPVD. We studied 23 patients with chronic liver disease to determine the prevalence of positive CE echocardiography suggesting the presence of IPVD and its relationship to arterial blood gases. None of our patients had schistosomal cor pulmonale. Five [21.7 percent] of.23 patients were hypoxemic [PaO 2<70mm Hg]. Eighteen patients [79.3 percent] had PaO 2>70mm Hg. Positive CE echocardiograms suggesting IPVD were found in 6 [26.08 percent] of 23. Three [16.7 percent] of the 18 patients with PaO 2>7Omm Hg had positive CE echocardiograms. Three [60 percent] of the five hypoxemic patients had positive CE echocardiograms. Patients with positive CE echocardiograms using indocyanine green [ICG] dye solution as a contrast were the same patients who had positive CE echocardiograms using isotonic saline solution alone as a contrast. No significant difference in the mean value of PaO 2 was noted between patients with positive and negative CE echocardiograms. We conclude that for our group of patients with chronic liver diseases, [1] IPVD as suggested by CE echo-cardiography were common [26.08 percent], [2] positive CE echocardiography could be documented in patients who were not hypoxemic [16.7 percent], [3] isotonic saline solution alone can be used as a reliable and cheap alternative for ICG dye solution in CE echocardiographic studies, [4] the presence of positive correlation between IPVD and spider naevi and esophageal varices, and [5] the absence of correlation between the Child's classification of liver dysfunction and the presence of IPVD

Glomerular lesions causing nephrotic syndrome [light microscopic findings] in 75 adult patients

This study includes seventy five adult patients of Nephrotic syndrome who underwent successful Renal Biopsy in order to determine the Glomerular pathology on light microscopy. More than 90% patients had primary glomerular lesions and the rest had secondary glomerular involvement. Focal and segmental proliferative glomerulonephritis [38%] and membranous glomerulonephritis [30%] were found to be the commonest lesions. Diabetes was the commonest [5%] cause of secondary glomerular lesions

Epidemiology of hepatitis delta virus infection in HBs Ag positive patients

Over a period of three years in Medical Unit I Civil Hospital Karachi, 230 patients screened positive for HBsAg, out of these 52 patients showed up anit-Delta antibodies giving a prevalence of 22.6 percent. 45/52 i.e. 86.53 percent were male and 7/52 [13.47 percent] were female thus indicating a male predominance. All age groups are affected by HDV infection, but prevalence was highest in patients in the sixth decade followed by the third decade. Meticulous history taking showed the probable routes of transmission. 16/52 [30.7 percent] revealed a history of parenteral injections, 10/52 [19.32 percent] had undergone a blood transfusion, 6/52 [11.53 percent] were drug addicts; 6/52 [11.53 percent] revealed sexual promiscuity, and 2/52 [3.82] patients underwent hamodialysis. In addition, majority of patients with evidence of HDV infection came from rural Sindh or far flung areas of Baluchistan. In conclusion, prevalence of HDV infection was found to be higher than that reported earlier from western countries and equal to or even higher than other Afro-Asian countries. The association of infection with probable routes of transmission is very strong in our patients. Patients from rural areas are more prone to develop this sinister infection