Nail Folds Capillaries Abnormalities Associated With Type 2 Diabetes Mellitus Progression and Correlation With Diabetic Retinopathy.

Background: Diabetic retinopathy (DR) is an important microvascular consequence of long-term type 2 diabetes mellitus (T2DM), and it can lead to blindness if not properly diagnosed and managed. Nailfold video capillaroscopy (NVC) is a non-invasive technique for observing capillary microvasculature. Aim: We aimed to evaluate the nail folds capillaroscopic alterations in patients with T2DM by NVC and correlated the results to DR, and their relation to disease duration and hemoglobin A1c (HbA1c). Methods: This cross-sectional study enrolled 62 cases with T2DM (as per the American Diabetes Association criteria). All patients were subjected to NVC and ophthalmological assessment. Results: NVC revealed that Patients with DR showed significantly higher frequencies of tortuous capillaries, branched capillaries and precapillary edema versus non-DR patients with P < .05. The DR patients with longer disease duration (15-20) years had significantly higher frequencies of branched capillaries, tortuous capillaries, microhemorrhages, and dilated apical capillaries. The frequency of tortuosity and precapillary edema were significantly higher in patients with poor glycemic control. The increased capillary width and branched capillaries were detected as predictors of DR in multivariate analysis. Conclusion: NVC is a cost-effective, quick, safe, simple, non-invasive, and newly emerging tool to assess the capillaroscopic alterations in diabetic patients as an indicator of severity of DR.

Novel thiazolidine derivatives as potent selective pro-apoptotic agents.

A series of 2-arylthiazolidine-4-carboxylic acid amide derivatives were synthesized and their cytotoxic activity against three cancer cell lines (PC-3, SKOV3 and MDA-MB231) was evaluated. Various structural modifications were tried including modifications of the length of the amide chain and modifications of the 2-aryl part using disubstituted phenyl and thiophene derivatives. The structure activity relationship was evaluated based on the in vitro biological evaluation against the above mentioned three cancer cell lines. The most selective compounds towards cancer cells were further evaluated against DLD-1, NCI-H520, Du145, MCF-7 and NCI-N87 cancer cells. The dodecyl amide having the 4-bromothienyl as the 2-aryl, compound 2e, exhibited the highest selectivity for cancer cells vs non-tumor cells. Mechanistic studies of the anticancer effect of compound 2e in prostate cancer PC-3 and colorectal cancer DLD-1 cells revealed that 2e could prevent the cell cycle in the G0/G1 phase by up-regulating the expression of p21 and reducing the expression of CDK2 and cyclin E. It increased the pro-apoptotic protein Bax and cleaved caspase 3, and down-regulated the expression of anti-apoptotic protein Bcl-2 to induce apoptosis. In addition, 2e also downregulated AKT, N-cadherin, and vimentin proteins expression giving indication that 2e inhibit the PI3K/AKT pathway to regulate cell cycle arrest and induce apoptosis, and can regulate the expression of epithelial-mesenchymal transition-related proteins.

The Efficacy of Citrus maxima Peels Aqueous Extract Against Cryptosporidiosis in Immunecompromised Mice.

INTRODUCTION:  Cryptosporidiosis is an opportunistic globally distributed parasitic disease caused by protozoan Cryptosporidium where its development is closely related to the host's immune status. New therapeutic agents are a high priority as chemotherapeutics are impractical and vaccines are unavailable for young as well as immune-compromised patients or animals. The current study was designed to evaluate the therapeutic effect of the internal white (albedo) and external yellow (flavedo) peels of Citrus maxima (C. maxima) as an alternative medicinal plant. MATERIALS AND METHODS : Parasitological examination for oocysts in the stool was determined. Histopathological alterations and immunohistochemical expression of APC and cyclin D1 as well as an assessment of interferon-γ (IFN-γ) and interleukin 1ß (IL-1ß) in ileal tissues was carried out. In addition, the biochemical examination of serum albumin, globulin and liver enzymes were evaluated. Results revealed a significant decrease of oocysts count correlated with an amelioration of histopathological and immunohistochemical changes in ileal tissue with an enhancement of liver enzymes and inflammatory cytokines levels. CONCLUSION:  It could be concluded that treatment with C. maxima peel extracts have a potential therapeutic and an immunoregulatory efficacy against Cryptosporidiosis. Obtained results showed that the white peel was found to have more immunological effect that could significantly enhance inflammatory cytokines response towards normal status. Hence, it can be used in the daily animal diet to give protective effects against infection.

Serum uric acid as a predictor for nephritis in Egyptian patients with systemic lupus erythematosus.

OBJECTIVE: Lupus nephritis (LN) is closely associated with hyperuricemia, and uric acid is considered a risk factor for renal involvement in systemic lupus erythematosus (SLE). This study aimed to examine the association between serum uric acid (SUA) level and LN development and progression in SLE patients with normal renal function. METHODS: A total of 60 SLE patients with normal renal function from Ain Shams University Hospital were selected and assigned to group 1 (30 patients with LN) and group 2 (30 patients without LN). All patients were subjected to history taking, clinical examination, disease activity assessment based on SLE disease activity index (SLEDAI) and renal SLEDAI (SLEDAI-R) scores, and laboratory investigations, including as SUA, complete blood count, blood urea nitrogen (BUN), serum creatinine, creatinine clearance, urine analysis, protein/creatinine ratio, 24-h urinary protein excretion, Antinuclear antibodies (ANA), anti-dsDNA antibody, and serum complement (C3, C4). RESULTS: Disease duration, SLEDAI score, and SUA level were higher in group 1 than in group 2 (p < 0.001). SUA level was positively correlated with SLEDAI and SLEDAI-R scores, proteinuria, urinary casts, renal biopsy class, disease activity and chronicity indices, BUN level, and serum creatinine level but was negatively correlated with creatinine clearance (p < 0.05). SUA was a predictor of LN development in SLE patients (sensitivity, 83.3%; specificity, 70%). CONCLUSION: SUA is associated with the development of lupus nephritis in patients with normal kidney function also SUA in-dependently correlated with disease activity and chronicity in LN.

Nerve Sheath Myxoma: A rare tumor, a case report and literature review.

INTRODUCTION: Nerve Sheath Myxoma is a rare benign nerve sheath tumor, commonly seen in young adults. Patients usually present with a small nodule commonly affecting upper and lower limbs. Nerve Sheath Myxoma has not been reported in children below the age of 1 year. CASE PRESENTATION AND METHODS: We present the first reported case of Nerve Sheath Myxoma (NSM) in the hand in a 4-month old child in line with the SCARE 2018 criteria. DISCUSSION: NSM is difficult to diagnose using standard imaging technique; Magnetic Resonance Imaging (MRI) and Ultrasonography (USS) cannot differentiate it from vascular anomalies. CONCLUSION: Soft tissue tumors in the hand of pediatric population are difficult to diagnose. Formal excision of the tumor by a specialized pediatric hand surgeon and histopathological analysis were the only avenue to correctly diagnose the NSM.

Gamma Radiation-Attenuated Toxoplasma gondii Provokes Apoptosis in Ehrlich Ascites Carcinoma-Bearing Mice Generating Long-Lasting Immunity.

PURPOSE: Pathological angiogenesis and apoptosis evasions are common hallmarks of cancer. A different approach to the antitumor effect of parasitic diseases caused by certain protozoans and helminthes had been adopted in recent years as they can affect many cancer characteristics. The present work is an attempt to assess the effect of gamma radiation-attenuated Toxoplasma gondii ME49 as an antiapoptotic and angiogenic regulator modifier on tumor growth aimed at improving cancer protective protocols. METHODS: Attenuated Toxoplasma gondii ME49 was administered orally to mice 2 weeks before inoculation with Ehrlich ascites carcinoma to allow stimulation of the immune response. Hepatic histopathology and immune responses were determined for each group. RESULTS: Marked suppression of the tumor proliferation with induction of long-lasting immunity by stimulating interferon γ and downregulating transforming growth factor ß. The level of tumor promoting inflammatory markers (STAT-3 and tumor necrosis factor α), the angiogenic factors (vascular endothelial growth factor A, integrin, and matrix metallopeptidase 2 and matrix metallopeptidase 9), as well as nitric oxide concentration were significantly decreased. This was collimated with an improvement in apoptotic regulators (cytochrome-c, Bax, Bak, and caspase 3) in liver tissues of vaccinated mice group compared to Ehrlich ascites carcinoma-bearing one. Moreover, the histopathological investigations confirmed this improvement. CONCLUSION: Hence, there is an evidence of potency of radiation attenuated Toxoplasma vaccine in immune activation and targeting tumor cell that can be used as a prophylactic or an adjuvant in combination with chemotherapeutic drugs.

Immunomodulatory activity of gamma radiation-attenuated Toxoplasma gondii in adjuvant arthritic mice.

There is growing evidence that some parasitic infections can impact a variety of autoimmune diseases by disease-inducing or protecting capacities. Anti-inflammatory molecules secreted by Toxoplasma gondii and other parasites are capable of preventing some autoimmune disease like arthritis, lupus nephritis and systemic lupus erythematosus by acting on the immune system. Here we aimed to evaluate the protective efficacy of vaccination with Toxoplasma gondii (T. gondii), either gamma radiation-attenuated or not, on an adjuvant arthritis mouse model. Forty female Swiss albino mice were conducted in experiment divided into normal control; mice were injected with Complete Freund's adjuvant (CFA) into the right hind paws; mice vaccinated with irradiated T. gondii in the 3rd group and un-irradiated T. gondii in the 4th group then were injected two weeks later with CFA. Histopathological changes and IL-17, STAT6 and ROR-γ levels in the joints, as well as serum survivin and Anti-CCP, were evaluated. Also, the splenic production of TGF-ß1, TGF-ßR, IL-23, IL-1ß, IFN-γ, TFN-∞, NFKß, MMP1 and MMP3 were assessed. Results exhibited an enhancement of the histopathological changes with diminished the rise of IL-17, STAT 6 and ROR- γ within the joints of both vaccinated groups. Also, serum survivin and Anti-CCP, as well as splenic inflammatory cytokines were reduced. It can be concluded that vaccination with un-irradiated or radiation-attenuated T. gondii exerted a protective effect against adjuvant arthritis with better pathological achievement in the radiation-attenuated vaccinated group. Using gamma radiation-attenuated parasite to exclude the delirious effects of imposing infection of live one may pave the way to new preventative modality against rheumatoid arthritis.

Vaccination with gamma radiation-attenuated Toxoplasma gondii protects against ovarian infiltration in mice-bearing Ehrlich ascites carcinoma.

Purpose: Cancer is one of the most common causes of mortality and morbidity worldwide. Vaccines have been emerged as an attractive approach for their capacity of eliciting long-term immune response targeting cancer cells. Attenuated avirulent Toxoplasma gondii stimulate immunity and activate antitumor cells thereby eliciting rejection of some established cancer. The purpose of this study was to evaluate the antitumor-protective capacity of vaccination with gamma radiation-attenuated T. gondii against ovarian penetration in Ehrlich ascites carcinoma (EAC)-bearing mice.Materials and methods: Forty-five mice were randomly divided into three groups as follows: nontumor-bearing (normal control); EAC-bearing group (EAC); and mice vaccinated orally with gamma radiation-attenuated T. gondii then inoculated 2 weeks later with EAC (TG + EAC). Survival rate, serum interleukin-12 (IL-12), and levels of IFN-γ mRNA, CD4, and CD8 in ovarian tissues homogenate were assessed. Also, ovarian histopathology and immunohistochemical expressions of metalloproteinase-2, CD34, and vimentin were determined.Results: The group vaccinated with attenuated T. gondii showed significantly increased survival rates, serum IL-12, and levels of IFN-γ, CD4, and CD8 in ovarian tissue homogenates as well as an enhancement of histopathological and immunohistochemical changes compared to EAC-bearing group.Conclusion: Vaccination with gamma radiation-attenuated T. gondii has the capacity to supply immunoprotective impact against ovarian invasion in EAC-bearing mice.

Blood group antigen-Binding Adhesion2 (BabA2) gene in gastric tissue biopsies as a diagnostic biomarker for Helicobacter pylori infection.

BACKGROUND: The Lewis (b) blood group antigen-Binding Adhesion2 (BabA2) has been reported to mediate the attachment of H. pylori to human. AIM: assessment the diagnostic potential of detection of (BabA2) gene compared with immunostaining of Lewis (b) by specific mouse monoclonal antibodies in gastric biopsies from Egyptian Patients as a diagnostic maker for Helicobacter pylori infection. MATERIALS AND METHODS: Fifty untreated patients suffering from dyspeptic complaints were enrolled in this study and underwent for upper gastro-duodenal endoscopy. Biopsies were taken for histological examination by (H&E) and immunohistochemical analysis for Lewis b by specific mouse monoclonal antibodies, and scoring of Lewis b expression in gastric tissue biopsy as well as molecular detection of BabA2 gene of H. pylori by PCR. Biochemical analysis was performed to detect the presence of H. pylori urease activity using Rapid Urease Test (RUT). RESULTS: Out of 50 gastric biopsies, 41 biopsies were positive for histological, Immunostaining for Lewis b expression and urease activity test (RUT) for H pylori. RUT showed a sensitivity of 87.8%, specificity 88.9%, positive predictive value (PPV) 97.2%, and negative predictive value (NPV) 61.5%. BabA2 gene results revealed that, out of 41 positive biopsied cases, 39 (95.1%) were positive by the PCR test for BabA2 gene. And all 9 negative biopsies (100%) for H pylori negative for BabA2gene so the sensitivity and specificity of BabA2 gene detection in gastric biopsies by PCR were 95.1% and 100%; respectively. CONCLUSION: BabA2 gene detection in gastric tissue biopsies could be suggested as a diagnostic biomarker to be included among the other biomarkers routinely performed for clinical diagnosis of H. pylori infection.

Anti-Toxoplasma antibodies in Egyptian rheumatoid arthritis patients.

OBJECTIVE: To assess seroprevalence of anti-Toxoplasma gondii antibodies; both IgG and IgM in Egyptian rheumatoid arthritis (RA) patients versus a non-RA group and to compare anti-Toxoplasma antibodies seroprevalence among RA patients receiving traditional treatment and RA patients treated with biologic drug. METHODS: 60 RA patients and 60 healthy controls were enrolled in the study. Patients were categorized into two groups: one group included 30 patients receiving disease modifying anti-rheumatic drugs (DMARDs), while the other group included 30 patients receiving biologic agent, infliximab, a TNF-α antagonist. Serum samples of all investigated persons were examined for anti-Toxoplasma antibodies. RA activity markers including rheumatoid factor, anti-cyclic citrullinated protein antibodies, C reactive protein, ESR in addition to disease activity score 28 (DAS28) of RA patients were also evaluated to explore their association with Toxoplasma seropositivity. RESULTS: Anti-Toxoplasma IgG antibodies were detected among 46/60 RA patients (76.7%) versus 29/60 controls (48.3%), (p = 0.001). Anti-Toxoplasma IgG titre was higher among RA group [median, (range) = 232.940 (8.949-653.242) IU/ml] than among controls [median, (range) = 68.820 (2.450-318.945) IU/ml], (p < 0.001). No difference was detected among RA patients either on traditional or biologic treatment regarding anti-Toxoplasma IgG antibodies. No positive anti-Toxoplasma IgM was detected. A positive correlation was detected between anti-Toxoplasma IgG titre and disease activity markers. CONCLUSION: Higher seroprevalence of anti-Toxoplasma IgG antibodies among RA patients compared to controls reflects an association between latent Toxoplasma infection and RA. Our findings support previous studies and necessitate future large-scale studies to elucidate the exact role of Toxoplasma whether a trigger of autoimmunity in RA or an effect of immunosuppression.

Bone mineral density changes in patients with recent-onset rheumatoid arthritis.

BACKGROUND: Osteoporosis and related fragility fractures are one of the most common complications seen in patients with rheumatoid arthritis (RA) and dramatically affect quality of life. OBJECTIVE: To evaluate changes in bone mineral density in patients with recent onset rheumatoid arthritis (<1 year) and its correlation if any with a modified DAS-28 score and simple erosion narrowing score (SENS). METHODS: This study included 30 patients with recent-onset rheumatoid arthritis fulfilling the new American College of Rheumatology/European League Against Rheumatism diagnostic criteria for rheumatoid arthritis and 20 healthy volunteers as controls. All were subjected to a complete blood count, erythrocyte sedimentation rate, C-reactive protein, liver function tests, renal function tests, rheumatoid factor, and plain x-rays of the hands and feet. Dual-energy x-ray absorptiometry DEXA was used to measure bone mineral density (BMD) of the left proximal femur, lumbar spine (L1-L4), and lower distal radius at the time of recruitment. RESULTS: In the RA patients, 13.3% had osteoporosis, 50% had osteopenia, and 36.7% had normal BMD. The most common site of osteoporosis was the lumbar spine (four patients, 13.3%) followed by the femur (two patients, 6.6%), and forearm (only one patient, 3.3%). There was a significantly higher percentage of osteoporosis among RA males than females and the difference was statistically significant (P = 0.009). Osteoporosis was more common in patients treated with corticosteroids and disease modifying antirheumatic drugs (DMARDs) than in patients treated with only nonsteroidal anti-inflammatory drugs (P = 0.004). Higher disease activity (DAS-28) was found in RA patients with osteoporosis compared to RA patients with normal BMD or osteopenia, but the difference was not statistically significant. Osteoporotic RA patients were found to have a higher SENS score for radiological damage than nonosteoporotic ones. CONCLUSION: BMD changes do occur in patients with early RA, and are not necessarily correlated with disease activity (DAS-28). However, a significant negative correlation was found between BMD and the score of radiological damage (SENS). Dual energy x-ray absorptiometry is an important investigation to assess BMD in early RA patients.