Vitamin E ameliorates alterations to the articular cartilage of knee joints induced by monoiodoacetate and diabetes mellitus in rats.

We recently reported an animal model of osteoarthritis (OA) induced by a combination of the chondrocyte glycolysis inhibitor, monoiodoacetate (MIA) and the agent that induces diabetes mellitus, streptozotocin (STZ). Here we investigated the potential protective effect of the antioxidant and anti-inflammatory agent, vitamin E against MIA+STZ-induced OA. Therefore, rats were either injected once with MIA (2 mg/50 µL) + 65 mg/kg STZ before being sacrificed after 8 weeks (model group) or were treated immediately after MIA+STZ injections with vitamin E (600 mg/kg; thrice a week) before being sacrificed after 8 weeks (treatment group). Using scanning and transmission electron microscopy examinations, we observed in the model group a substantial damage to the articular cartilage of the knee joint as demonstrated by the destruction of the chondrocytes, territorial matrix, disrupted lacunae, collagen fibers, and profound chondrocyte ultrastructural alterations such as degenerated chondrocyte, irregular cytoplasmic membrane, damaged mitochondria and rough endoplasmic reticulum, vacuolated cytoplasm, presence of lipid droplets and different sizes of lysosomes, which were substantially but not completely protected by vitamin E. H&E stained sections of knee joint articular cartilage showed that MIA+STZ induced damage to the chondrocyte and territorial matrix. Vitamin E also significantly (p < .05) inhibited MIA+STZ-induced blood levels of the inflammatory biomarkers, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) that are known to be modulated in OA and diabetes. We conclude that vitamin E protects against MIA+STZ-induced knee joints injuries in rats, which is associated with the inhibition of biomarkers of inflammation.

Insulin protects against hepatocyte ultrastructural damage induced by type 1 diabetes mellitus in rats.

Diabetic complications that affect vital organs such as the heart and liver represent a major public health concern. The potential protective effects of the hormone insulin against hepatocyte ultrastructural alterations induced secondary to type 1 diabetes mellitus (T1DM) in a rat model of the disease have not been investigated before. Therefore, rats were injected once with 65 mg/kg streptozotocin (T1DM group) and the protection group (T1DM+Ins) received a daily injection of insulin 48 h post diabetic induction by streptozotocin and continued until being sacrificed at week 8. The harvested liver tissues were examined using transmission electron microscopy (TEM) and blood samples were assayed for biomarkers of liver injury enzyme, glycemia, lipidemia, inflammation, and oxidative stress. TEM images showed that T1DM induced profound hepatocyte ultrastructural alterations as demonstrated by pyknotic nucleus, condensation of chromatin, irregular nuclear membrane, swollen mitochondria, dilated rough endoplasmic reticulum, damaged intercellular space, and accumulation of few lipid droplets inside the hepatocyte cytoplasm, which were substantially protected with insulin. In addition, the blood chemistry profile complements the TEM data as demonstrated by an increase in serum levels of alanine aminotransferase (ALT), dyslipidemia, C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and malondialdehyde (MDA) by T1DM that were significantly (p < 0.05) reduced with insulin injections. Thus, we conclude that insulin effectively protects against T1DM-induced liver injury in rats for a period of 8 weeks, possibly due to the inhibition of inflammation, oxidative stress, and dyslipidemia.

Development of a rat model of knee osteoarthritis by a combination of monoiodoacetate and streptozotocin / Desarrollo de un modelo de rata de osteoartritis de rodilla por una combinación de monoiodoacetato y estreptozotocina

SUMMARY: Osteoarthritis (OA) caused by ageing joints or as a secondary complication of diabetes is a common health problem. We sought to develop an animal model of OA induced by a combination of the chondrocyte glycolytic inhibitor mono-iodoacetate (MIA) and streptozotocin (STZ), the agent that induces diabetes mellitus. We then hypothesized that the extent of damages to the knee joint induced by this model can be greater than OA induced by either MIA or STZ. Rats were either injected with MIA (model 1) or STZ (model 2) or both agents (model 3). After 8 weeks, harvested tissues from the knee joint of these groups were examined using scanning and transmission electron microscopy. In addition, blood samples were assayed for tumor necrosis factor alpha (TNF-α) and interleukin -6 (IL-6) that are known to be modulated in OA and diabetes. Compared to control group, substantial damages to the articular cartilage of the knee joint were observed in the three models with the severest in model 3. In addition, rats in model 3 showed significant (P<0.0001) increase in TNF-α and IL-6 compared to model 1 and 2. Thus, we have developed a new model of knee OA in rats that mimics a type of OA that is common among elderly people who have both, "ageing" joints and diabetes.

RESUMEN: La osteoartritis (OA) es un problema generalizado de salud a causa de un envejecimiento de las articulaciones, o bien de una complicación secundaria de la diabetes. El objetivo de este estudio fue desarrollar un modelo animal de OA inducido por una combinación dos drogas, un inhibidor de los condrocitos glucolíticos, el mono-iodoacetato (MIA), y la estreptozotocina (STZ), agente que induce la diabetes mellitus. Se consideró como hipótesis que el alcance de los daños a la articulación de la rodilla inducida por este modelo puede ser mayor que la OA inducida por MIA o STZ. Las ratas fueron inyectadas con MIA (grupo 1) o STZ (grupo 2) o ambos agentes (grupo 3). Se extrajeron muestras de la articulación de la rodilla de estos grupos al término de 8 semanas, y se examinaron mediante microscopía electrónica de barrido y de transmisión. Además, se analizaron muestras de sangre para el factor de necrosis tumoral alfa (TNF-α) e interleucina-6 (IL-6), que están moduladas en OA y en la diabetes. En comparación con el grupo control, se observaron daños sustanciales en el cartílago articular de la articulación de la rodilla en los tres modelos, encontrándose los daños más severos en el grupo 3. Además, las ratas del grupo 3 mostraron un aumento significativo (P <0,0001) de los niveles de TNF-α e IL- 6, en comparación con los grupos 1 y 2. Hemos desarrollado un nuevo modelo de OA de rodilla en ratas que imita un tipo de OA el cual, además de la diabetes, es común entre las personas mayores con un nivel importante de daño en las articulaciones.

Swollen eyelid reveals multiple intracranial hydatid cysts associated with a palpebral cyst.

We report a case of a hydatid cyst of the eyelid in a 12-year-old boy associated with cerebral involvement. The patient was initially treated by neurosurgeons for brain cysts. The course after an interval of two months was marked by regression of the palpebral cyst on albendazole.

Coexistence of sickle cell nephropathy and lupus nephritis in a Sudanese child.

In spite of the wide distribution of sickle cell disease (SCD) in Africa, an association with systemic lupus erythromatosis (SLE) is seldom reported. This may be due to the poor association between the two diseases or the high prevalence of missed cases. Progressive renal injury is prominent in both SCD and SLE. In this communication, we are presenting a case of an 11-year-old male who presented with sickle cell nephropathy that manifested as nephrotic syndrome with no response to conservative therapy, alongside unexplained massive hemolysis. His renal biopsy proved SLE superimposed on sickle cell nephropathy. We are stressing the importance of considering alternate disease processes in patients with SCD when symptoms change or when there is an atypical clinical course.

Treatment-based strategy for the management of post-kala-azar dermal leishmaniasis patients in the Sudan.

UNLABELLED: Post-kala-azar dermal leishmaniasis (PKDL) is a dermatosis that affects more than 50% of successfully treated visceral leishmaniasis (VL) patients in Sudan. PKDL is considered an important reservoir for the parasite and its treatment may help in the control of VL. Currently, treatment is mainly with sodium stibogluconate (SSG), an expensive and fairly toxic drug and without universally in treatment protocols used. A literature review, a consensus of a panel of experts, and unpublished data formed the basis for the development of guidelines for the treatment of PKDL in the Sudan. Six treatment modalities were evaluated. Experts were asked to justify their choices based on their experience regarding of drug safety, efficacy, availability, and cost. The consensus was defined by assigning a categorical rank (first line, second line, third line) to each option. Regarding the use of AmBisome the presence of the drug in the skin was confirmed in smears from PKDL lesions. RECOMMENDATIONS: AmBisome at 2.5 mg/kg/day/20 days or SSG at 20 mg/kg/day/40 days plus four/weekly intradermal injection of alum-precipitated autoclave L. major vaccine are suggested as first- and second-treatment options for PKDL in the Sudan, respectively. SSG at 20 mg/Kg/day/60 or more days can be used if other options are not available.

[Orbital schwannoma: clinical, imaging and surgical features]. / Schwannome orbitaire : aspects cliniques, radiologiques et chirurgicaux.

INTRODUCTION: Schwannoma, or peripheral glioma, is a rare tumor of the orbit (1% of orbital tumors). Its diagnosis remains difficult and can be established only by histological analysis. We discuss through this case report the clinical, radiological and surgical features of this tumor. OBSERVATION: We report the case of a young 38-year-old woman with high myopia and no specific medical history, presenting with a rapidly progressive decrease in visual acuity of the right eye, associated with swelling of the supero-lateral orbit, and eccentric, non-pulsatile, ipsilateral proptosis. Clinical examination of the right eye revealed corrected visual acuity of 20/40, mobile swelling near the lacrimal gland and limitation of elevation and abduction. Slit lamp exam revealed secondary central corneal degeneration. Fundus exam was remarkable for stage I optic nerve head edema. Examination of the left eye was unremarkable. Orbital CT revealed a mass of 21.3mm×14.8mm, hypodense and heterogeneous, attached to the lacrimal gland, displacing the globe downward and inward, enhancing with contrast and without bone erosion. Excision of the tumor and the remaining stump of the gland was performed through a subciliairy skin incision followed by histological analysis confirming the diagnosis of schwannoma. No recurrence was noted after a follow-up of a year and a half. CONCLUSION: Schwannoma is a rare tumor of the orbit. Its clinical and radiological diagnosis is always difficult. Only histological study allows confirmation of the diagnosis. The absence of recurrence is dependent upon total surgical excision.

Schistosomiasis of the spinal cord: report of 5 cases from Sudan

Schistosomiasis of the spinal cord is an uncommon but potentially curable form of schistosomiasis, if diagnosed and managed early. The spinal cord is more frequently affected in Schistosomo mansoni or S. hoemotobium infections. This paper describes the clinical manifestations, diagnosis and management of schistosomiasis of the spinal cord in 5 patients attending Shaab and Ibn Khuldoun Hospitals, Khartoum from 1997 to 2007. There were 4 males and 1 female aged 9-45 years. They presented with symptoms and signs due to cord compression at the lower thoracic and lumbar vertebrae. Imaging studies revealed intramedullary masses compressing the cord. Biopsy showed ova of 5. mansoni with surrounding inflammatory reaction. The cord showed demyelination nearthe ova and an associated inflammatory reaction. Patients responded well to surgical decompression and treatment with praziquantel and oral steroids

Castleman's disease in a kidney failure patient diagnosed incidentally during transplantation.

INTRODUCTION: Castleman's disease is a rare lymphoid disorder. It comprises two pathological entities. These are the hyaline-vascular type which is usually localized (uni-centeric) and the plasma-cell type which is usually multicenteric and rather aggressive. CASE REPORT: Here we present a 53 years old Sudanese male who underwent kidney transplantation in August 2009 from a related live-donor. During transplantation, he was accidently found to have an abnormal looking lymph node at the site of the graft bed. The lymph node was totally excised and sent for histopathology. Based on the histopathological examination, the diagnosis of Castleman's disease of the hyaline vascular type was made. The patient gained normal graft function and was maintained on tacrolimus, azathioprine and prednisolone. He maintained normal graft function for more than twelve months post transplantation with a serum creatinine level of 0.9 mg/dl. He remained free from recurrence of Castleman's disease during the follow up period. CONCLUSION: Unicenteric Castleman's disease may be completely asymptomatic. Surgical excision of the lesion was curative for our patient despite maintenance on immunosuppression.

The safety and efficacy of itraconazole for the treatment of patients with eumycetoma due to Madurella mycetomatis.

This prospective study aimed to determine the safety and efficacy of itraconazole for the treatment of patients with mycetoma due to Madurella mycetomatis. The study consisted of 13 patients with confirmed disease; all were treated with oral itraconazole in a dose of 400mg daily for three months after which the dose was reduced to 200mg daily for nine months. All patients showed good clinical response to 400mg itraconazole daily, but when the dose was reduced to 200mg daily, the clinical response was gradual and slow. Post-treatment surgical exploration showed that, in all patients, the lesions were well localized, encapsulated with thick capsule and they were easily removed surgically. In all these lesions, grains colonies were encountered and they were viable on culture. Post-operative biopsies showed no significant changes in the morphology of the grains. A constant finding was the presence of between 5-7 grains in a single cavity walled by fibrous tissue. The reaction surrounding the grains was a Type I tissue reaction characterized by a neutrophil zone around grains. Patients were followed up post-operatively for variable periods (range 18-36 months) and only one patient had recurrence. Initial pre-operative treatment with itraconazole may be recommended for eumycetoma patients to enhance lesions encapsulation and localization which can facilitate wide local excision to avoid unnecessary massive mutilating surgery and recurrence.

Gastrointestinal stromal tumours (GISTs): case report and review of the literature.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract, the majority of which is KIT (CD117) positive. In this case report, we describe a case of recurrent and metastatic GIST who presented with hepatic and brain metastases. Despite the patient's GISTs was negative for c-Kit (CD 117), he responded to imatinib mesylate (Glivec) treatment with complete resolution of his liver and brain lesions. The patient has been and still in complete remission for 18 months of follow-up.

Nasopharyngeal cancer in Sudan: epidemiology, clinical and histological characteristics.

OBJECTIVES: To study the epidemiology, clinical features, staging, etiology and pathology of nasopharyngeal cancer in Sudan. STUDY DESIGN: This is a retrospective study. SETTING: Ear, Nose and Throat Department Khartoum Teaching Hospital, Khartoum City, Sudan. SUBJECTS AND METHODS: Patients suspected to have nasopharyngeal cancer were assessed during the period March 2004 to May 2010. Data from confirmed cases was obtained; it included clinical and epidemiological information. RESULTS: Three hundred and eighty five cases were studied. Bimodal age distribution of the disease was noted with two peaks, one at 15-19 years and one at 50-54 years. The male to female ratio was 2.6:1 and a distinct geographical distribution of the disease was noted, with clustering of cases in the towns of Dilling, Kadogli and the surrounding rural area of the Nuba Mountains. These areas in the Western States were reported to be of high background radiation due to naturally produced radioactive uranium. The Nuba tribe headed the list among other tribes, demonstrating a clear ethnic predilection. Sixty-eight cases presented at stage IV. There was a predominance of Type II (15.58%) and Type III (65.97%). Patients were treated by neoadjuvant chemoradiotherapy. CONCLUSIONS: NPC is an important form of cancer in Sudan. Some tribes are significantly more affected than others. Patients present with advanced disease. Environmental and genetic factors need further studies. Screening at risk populations that aim at early diagnosis and management of patients is recommended.

Surrogate markers of subtle renal injury in patients with visceral leishmaniasis.

Sudanese visceral leishmaniasis (VL) is a disease of children that is characterized by fever, hepatosplenomegaly, lymphadenopathy, pancytopenia, and renal injury. Microalbuminuria (MA) and urinary retinol binding protein (urRBP) are useful markers for glomerular and tubular dysfunctions, respectively. We report the prevalence of subtle renal injury in 88 parasitologically confirmed VL patients in a cross-sectional and hospital-based study. Blood and urine were collected before treatment for hematological, biochemical profiles in addition to MA and urRBP measurement using competitive solid phase, sandwich enzyme-linked immune sorbent assay (ELISA), and immunoturbidometry. All the patients had normal serum urea and creatinine levels and no detectable urRBP. However, 40% of the patients had MA detected by ELISA, and 42% were reactive with turbidometry. The sensitivity, specificity, positive and negative predictive values for MA turbidometric technique were calculated as 100%; 96%; 95% and 100%, respectively. In conclusion; subtle renal injury in VL is mainly glomerular. Turbidometry for MA measurement is a simple, inexpensive, sensitive, and specific technique with high predictive values.

Leishmania donovani: genetic diversity of isolates from Sudan characterized by PCR-based RAPD.

Drug unresponsiveness in patients with visceral leishmaniasis (VL) is a problem in many endemic areas. This study aimed to determine genetic diversity of Leishmania donovani isolates from a VL endemic area in Sudan as a possible explanation for drug unresponsiveness in some patients. Thirty clinically stibogluconate (SSG)-sensitive isolates were made SSG-unresponsive in vitro by gradually increasing SSG concentrations. The sensitive isolates and their SSG-unresponsive counterparts were typed using mini-circle kDNA and categorized using PCR-RAPD. All the isolates were typed as L. donovani, the resulting PCR-RAPD characterization of the SSG-sensitive isolates gave three distinct primary genotypes while, the SSG-unresponsive isolates showed only a single band. L. donovani isolates from eastern Sudan are diverse; this probably resulted from emergence of new L. donovani strains during epidemics due to the pressure of widespread use of antimonials. In this communication the possible role of isolates diversity in antimonial unresponsiveness and the in vitro changing PCR-RAPD band pattern in SSG-unresponsive strains were discussed.