Vitamin D status, vitamin D receptor gene polymorphism, and haplotype in patients with cutaneous leishmaniasis: Correlation with susceptibility and parasite load index.

BACKGROUND: CL endemicity was reported worldwide including in Saudi Arabia, imposing a major challenge on the health authorities. Vitamin D and its receptor (VDR) are key modulators of the immune response where the VDR is expressed. A remarkable lack of data exists in humans about the contribution of vitamin D and polymorphisms of the VDR gene in protozoan infections, especially cutaneous leishmaniasis (CL). OBJECTIVE: This is the first work conducted to assess the relationship between vitamin D status, polymorphisms of the VDR gene (BsmI, ApaI, TaqI, and FokI), and VDR haplotype with parasite tissue load and susceptibility to CL. METHODS: Fifty-two patients with confirmed CL (21 patients receiving vitamin D medication and 31 patients not receiving it) and 46 control subjects participated in this cross-sectional investigation. VDR genotyping was determined by restriction fragment length polymorphism analysis. Serum levels of 25-OH vitamin D were assessed using the ELISA method in all participants. The skin biopsy quantified the parasite load based on the Ridley parasitic index. RESULTS: The mean serum level of 25-OH vitamin D in CL patients who were not receiving vitamin D therapy was significantly lower compared to CL patients on vitamin D therapy and controls (p <0.001 for both) and CL patients with no history of vitamin D therapy had a significantly higher frequency of vitamin D deficiency compared to CL patients on vitamin D therapy and controls (p < 0.05). Compared to CL patients with no history of vitamin D therapy, CL patients receiving vitamin D therapy had a significantly lower mean size of the lesion and RPI (p = 0.02, .03 respectively). The frequency of genotype "aa" and its "a" allele in ApaI SNP of VDR was significantly lower in CL patients compared to controls (p = 0.006 and 0.03 respectively). However, patients with CL had a considerably greater frequency of the "A" allele than the controls (p = 0.03), suggesting its role in CL susceptibility. There was no statistically significant difference between the two groups in the genotype and allele frequency distributions of BsmI, TaqI, and FokI (p > 0.05). When compared to controls, CL cases had a considerably greater frequency of the "B-A-T-F" haplotype (p = 0.04), and a significantly lower frequency of the "B-a-T-F" haplotype (p = 0.01) suggesting that these haplotypes may have the potential susceptibility or protection against CL respectively. The "Aa" genotype in ApaI SNP of VDR had considerably lower levels of vitamin D with higher parasite load compared to the "AA" and: aa" genotypes (p = 0.02,0.02 respectively). A significant negative correlation was found between the parasite load and 25-OH vitamin D levels (r2 = -0.53, p< 0.001). CONCLUSIONS: According to these findings, vitamin D levels and "ApaI" VDR gene polymorphisms could affect the parasite load and susceptibility to infection, whereas BsmI, FokI, and TaqI polymorphisms did not. Correction of vitamin D levels may aid in CL management.

Anti-angiogenic and anti-proliferative activity of ziziphus leaf extract as a novel potential therapeutic agent for reducing hepatic injury in experimental hamster schistosomiasis.

BACKGROUND: Schistosomiasis is one of the most prevalent helminthic infections worldwide. Praziquantel (PZQ) resistance poses a possible danger to the disease's ability to be controlled. Little is known about the role of Ziziphus spina-christi leaf extract (ZLE) in the treatment of hepatic schistosomiasis. However, no study has explored ZLE's anti-angiogenic and anti-proliferative activity as a possible mechanism for reducing hepatic injury in this context. Therefore, this study aimed to evaluate the therapeutic potential of ZLE as an anti-angiogenic, and anti-proliferative agent in hamsters infected with S. mansoni. METHODS: Fifty hamsters were used and divided into 5 groups (10 hamsters each); noninfected untreated (controls), noninfected treated with ZLE, infected untreated, infected treated with PZQ- and infected treated with ZLE. Anti-angiogenic and anti-fibrotic effects of the drugs were assessed pathologically through the immunohistochemical expression of VEGF, Ki-67, and TGF ß1 in liver sections. Some oxidative stress parameters were measured in hepatic homogenates (NO, GSH, GST, and SOD), and serum liver enzymes were also assessed. RESULTS: A significant decrease in worm burden, granuloma size, granuloma area, and numbers in the ZLE- and PZQ-treated groups compared to the infected untreated group, and the decrease in granulomas number and tissue egg load was significantly lower in PZQ treated group compared to ZLE treated group (p<0.05). ZLE exhibited significant anti-angiogenic and anti-fibrotic effects on granulomas, illustrated by significantly lower expression of VEGF and TGF-ß1 than infected untreated and PZQ-treated groups. ZLE exhibits antiproliferative activity evidenced by a significant reduction of positive Ki-67 hepatocytes percentage compared to the infected untreated group. Moreover, ZLE exhibits potent antioxidant effects evidenced by a significantly lowered NO and conservation of hepatic GSH, GST, and SOD in hepatic homogenates compared to infected untreated and PZQ-treated groups (p<0.05). CONCLUSION: Our results point to ZLE as a promising hepatoprotective therapeutic tool in the treatment of schistosome hepatic fibrosis as it has anti-angiogenic, anti-proliferative, anti-fibrotic, and antioxidant effects in hamsters infected with S. mansoni, providing scientific support for its use in conventional medicine.

Toxoplasma and Toxocara seropositivity in juvenile idiopathic arthritis and its relation to disease activity and type of therapies.

Juvenile idiopathic arthritis (JIA) is the most frequently encountered autoimmune rheumatic disease in children. To our knowledge, this is the first study aimed to estimate the frequency of Toxoplasma gondii (T. gondii) and Toxocara seropositivity in JIA and assess its relation to the disease activity, IL-10 levels, and type of the received therapies. This study was conducted on 43 JIA patients and 50 cases as a control group. All participants were evaluated by disease activity score (JADAS-27), and the presence of specific IgG and IgM antibodies against T. gondii and IgG against Toxocara species using an enzyme-linked immunosorbent assay. IL-10 serum levels were measured using an ELISA kit. The results show that JIA patients have significantly higher seropositivity for anti-T. gondii IgG compared to control subjects (p = 0.02) and a non-significant difference for Toxocara seropositivity (p = 0.41). All participants were negative for IgM anti-Toxoplasma gondii. Demographic parameters did not significantly affect these seroprevalence frequencies (p > 0.05). IL-10 was significantly higher among JIA patients compared to controls (p = 0.007) and seropositive anti-T. gondii JIA exhibited significantly higher IL-10 levels compared to seronegative ones (p = 0.03). Seropositive anti-T. gondii IgG JIA patients had a significantly higher disease activity score (JADAS-27) than seronegative anti-T. gondii IgG cases (p = 0.02). There was a significant positive correlation between anti-T. gondii IgG and JADAS-27 score (p = 0.009). A significant association was detected between T. gondii infection and DMARDs including the biological therapies (p < 0.05). Overall, this study supports a possible association between T. gondii infection and JIA, IL-10, disease activity score, and DMARDs therapies. It is possible that IL-10 plays a role in the development of JIA and contributes to persistent asymptomatic infection with T. gondii in JIA patients. As a result, a recommendation for screening tests for T. gondii infection among JIA patients is crucial before and during commencing DMARDs therapies and closely monitoring early signs of infection.

Exploring digital technologies used in the design and manufacture of craniofacial implant surgical guides: A scoping review.

STATEMENT OF PROBLEM: Unlike intraoral implants, digitally planned surgical templates used for guiding the ideal position of the craniofacial implants are not well established, and clear methods and guidelines for their design and construction are lacking. PURPOSE: The purpose of this scoping review was to identify the publications that used a full or partial computer-aided design and computer-aided manufacture (CAD-CAM) protocol to create a surgical guide that achieves the correct positioning of craniofacial implants to retain a silicone facial prosthesis. MATERIAL AND METHODS: A systematic search was conducted in MEDLINE/PubMed, Web of Science, Embase, and Scopus for articles published before November 2021 in the English language. Articles needed to satisfy the eligibility criterion of in vivo articles that created a surgical guide with digital technology for inserting titanium craniofacial implants to hold a silicone facial prosthesis. Articles that inserted implants in the oral cavity or upper alveolus only and articles that did not describe the structure and retention of the surgical guide were excluded. RESULTS: Ten articles were included in the review; all were clinical reports. Two of the articles used a CAD-only approach alongside a conventionally constructed surgical guide. Eight articles described applying a complete CAD-CAM protocol for the implant guides. The digital workflow varied considerably depending on the software program, design, and retention of guides. Only 1 report described a follow-up scanning protocol to verify the accuracy of the final implant positions compared with the planned positions. CONCLUSIONS: Digitally designed surgical guides can be an excellent adjunct to accurately place titanium implants in the craniofacial skeleton for support of silicone prostheses. A sound protocol for the design and retention of the surgical guides will enhance the use and accuracy of craniofacial implants in prosthetic facial rehabilitation.

Seroprevalence of Toxoplasma gondii among hemodialysis patients: A possible link to main T-lymphocyte subsets levels and dialysis adequacy.

BACKGROUND: A high prevalence of Toxoplasma gondii infection has been reported in patients with hemodialysis (HD). However, a lack of data exists on the relationship between T lymphocyte subsets and dialysis adequacy. This study aimed to investigate the seroprevalence of Toxoplasma gondii infection among HD patients and its relation to T lymphocyte cells subsets, CD3+, CD4+, CD8+, CD4+/CD8+ ratio, and HD adequacy. METHODS: This cross-sectional comparative study was conducted on 92 subjects. Of them, 42 HD patients and 50 were control participants. Anti-Toxoplasma gondii IgG, IgM antibodies, the T lymphocyte cells subset CD3+, CD4+, CD8+, CD4+/CD8+ ratio, and adequacy of dialysis via calculation of Kt/V were detected for all subjects. RESULTS: The seropositivity for anti-Toxoplasma gondii IgG antibodies was significantly higher in HD patients 66.7% (28/42) compared to 34% in controls (17/50), (p = 0.0003). The main T lymphocyte subsets was significantly lower in HD compared to controls (p < 0.05). Seropositive HD patients exhibited statistically significantly lower T lymphocyte cell subsets and CD4+/CD8+ ratio compared to seronegative patients (p < 0.05). There was a negative correlation between anti-Toxoplasma gondii IgG level and T lymphocyte subsets and the CD4/CD8+ ratio. Binary logistic regression showed that CD4+ T cell significantly predicts Toxoplasma gondii susceptibility among HD patients (p = 0.03). The mean Kt/V index is significantly lower among seropositive HD patients compared to seronegative HD patients (1.05 ± 0.46, 1.41 ± 0.53, respectively, p = 0.03) with a significant negative correlation with anti-Toxoplasma gondii IgG level (p < 0.05). ROC curve analysis showed the CD4+ T cell % had the highest AUC value among HD patients (AUC= 0.88, p < 0.001). The Kt/V value of ≤ 0.8 significantly predicted susceptibility to Toxoplasma gondii infection among HD patients (AUC = 0.68, p = 0.03). CONCLUSION: The current study reinforces previous reports of a high prevalence of Toxoplasma gondii infection among HD patients. CD4+ T cell and Kt/V showed a good diagnostic performance in predicting susceptibility for Toxoplasma gondii infection in HD patients. Considering the clinical consequences caused by Toxoplasma gondii infection in these patients, regular screening and adequate HD are recommended.

Association between Toxoplasma gondii infection and metabolic syndrome in obese adolescents: A possible immune-metabolic link.

Background Toxoplasmosis as a global disease is considered as a triggering factor responsible for development of several clinical diseases. However, Toxoplasma gondii (T. gondii) is an understudied parasite of potential interest in obesity research. The current study aimed to explore the role of latent T. gondii infection in the pathogenesis of metabolic syndrome (MetS) in obese adolescents through studying the relationship between serum interferon-gamma [IFN-γ] and serum chemerin in context of MetS components. Methods Eighty-three obese adolescents were serologically screened for T. gondii-IgG antibodies and compared to 35 age-matched healthy T. gondii-seronegative controls. Participants were evaluated for anthropometric measurements, total-fat mass [FM], trunk-FM, serum lipid profile, IFN-γ, and chemerin levels. Homeostatic Model Assessment of insulin resistance (HOMA-IR) was calculated. Results The prevalence of MetS was significantly higher within obese T. gondii-seropositive group compared to obese T. gondii-seronegative group (P = 0.033). Seropositive obese MetS group displayed significantly higher trunk-FM, HOMA-IR, chemerin, and IFN-γ compared to seronegative obese MetS group. Serum chemerin and IFN-γ were strongly correlated (P < 0.001) and were positively correlated with BMI, WC, total-FM, trunk-FM, HOMA-IR, cholesterol, triglycerides and negatively correlated with HDLC. HOMA-IR was a common predictor for serum chemerin (P = 0.030) and IFN-γ (P < 0.001). Conclusions The study results suggest that T. gondii infection may exert an immune-metabolic effect that may have a potential role in the development of MetS among obese adolescents.

Evaluation of the efficacy of oral ivermectin in comparison with ivermectin-metronidazole combined therapy in the treatment of ocular and skin lesions of Demodex folliculorum.

OBJECTIVE: To evaluate the efficacy of ivermectin and combined ivermectin-metronidazole therapy in the treatment of ocular and skin lesions of Demodex folliculorum. METHODS: One hundred twenty patients with skin lesions and anterior blepharitis, whose infestation was treatment-resistant and who had a Demodex count >5 mites/cm² for skin lesions or ≥ 3 mites at the root of each eyelash, were recruited. The treatment regimens were ivermectin and ivermectin-metronidazole combined therapy. We enrolled 15 patients from each of four groups for each treatment regimen. Demodex was detected by standardized skin surface biopsy for skin lesions. Three eyelashes from each affected lower eyelid were epilated and examined. The study subjects were followed-up once a week for four visits. RESULTS: There was a difference in the mite count between the subgroups taking ivermectin and combined therapy during all follow-up visits. At the last visit, in the combined therapy subgroup, 1.7% of patients showed no clinical improvement, 26.7% showed a marked clinical improvement, and 71.6% showed complete remission. In those on the ivermectin regimen, 27 patients had a mite count >5 mites/cm², 21.7% showed no clinical improvement, 33.3% showed a marked improvement, and 45% showed complete remission. CONCLUSIONS: Combined therapy was superior in decreasing the D. folliculorum count in all groups and in reducing the mite count to the normal level in rosacea and in anterior blepharitis. On the other hand, the two regimens were comparable in reducing the mite count to the normal level in acne and peri-oral dermatitis lesions.