Human protozoa infection and dysplasia in ulcerative colitis: a neglected aspect in a prominent disease.

The chance of getting colorectal cancer (CRC) is higher in people with chronic ulcerative colitis (UC). The impact of parasitic infections on UC is underappreciated. The purpose of this study was to look into the effect of intestinal protozoal infections on the dysplastic changes generated by UC. The research included 152 adult patients with histologically confirmed UC and 152 healthy controls. Fecal samples were examined for the presence of parasites and fecal calprotectin (FC). The enzyme-linked immunosorbent assay measured serum anti-p53 antibodies (p53Abs) and metallothioneins (MTs). The advanced oxidation protein products (AOPPs) and reduced glutathione (GSH) levels were measured by a spectrophotometric method in all subjects. Serum C-reactive protein (CRP) and IL-6 were also measured. In addition, histopathological and immunohistochemical investigations of intestinal tissue were done. Our results exhibited significant increases in FC and CRP, IL-6, AOPPs, MTs, and p53Abs in ulcerative colitis patients with parasitic infections compared to those without parasites. In contrast, GSH levels showed a significant decrease in the same group compared with other groups. Histopathological and immunohistochemical assessments of intestinal tissue signified severe inflammation and strong expression of PD-L1 in patients with parasitic infections compared to others without parasitic infections. Our research indicated a greater frequency of intestinal protozoa in UC patients with elevated inflammatory and dysplastic biomarker levels. This suggests that these parasites may be involved in the etiology of chronic UC and the associated carcinogenetic process. This is the first report of a link between parasitic infections and dysplastic alterations in UC patients.

Hysteroscopic management versus ultrasound-guided evacuation for women with first-trimester pregnancy loss, a randomised controlled trial.

OBJECTIVE: We aimed to evaluate the hysteroscopic management of first-trimester pregnancy loss compared to surgical evacuation either blind or under ultrasonographic guidance . METHODS: This clinical trial included 315 women with first-trimester pregnancy loss, divided equally into three groups. Group 1 underwent traditional blind surgical evacuation, group 2 underwent ultrasound-guided evacuation, and group 3 underwent hysteroscopic management. All women were assessed for retained products, surgical complications, the need for further management, and pregnancy occurrence after evacuation within 2 years of follow up. RESULTS: The rate of presence of conception remnants and the need for further treatment was significantly higher in group 1 compared to groups 2 and 3 (4.8% vs. 0% vs. 0%, P = 0.012). The conception rate within 2 years was significantly lower in group 1 compared to groups 2 and 3 (57.4% vs. 73.2% vs. 82.7%, P = 0.002), and the duration needed to conceive was significantly prolonged in group 1 compared to groups 2 and 3 (9.8 vs. 8.3 vs. 6.9 months, P < 0.001). Interestingly, women who underwent hysteroscopic management needed a significantly shorter time to conceive than those who underwent ultrasound-guided evacuation (6.9 vs. 8.3 months, P = 0.006). CONCLUSIONS: Hysteroscopic management of first-trimester pregnancy loss was superior to ultrasound-guided surgical evacuation regarding the time interval to conceive. Both techniques were superior to the blind evacuation technique regarding removal of the whole conception remnants, need for further treatment and fertility outcomes. Clinical trial registration: It was first registered at ClinicalTrials.gov on 16/03/2017 with registration number NCT03081104.

A Notorious Trio! Inflammation, Metabolic Syndrome and Vitiligo.

Background: There is evidence to support that vitiligo is linked to metabolic syndrome (MS), confirming its systemic nature. However, the underlying pathogenic mechanisms remain unknown. Objectives: To reveal the possible association of MS with vitiligo. We also attempted to study the connection between some inflammatory markers and MS in vitiligo patients to evaluate their utility in predicting MS risk. Materials and Methods: The study included 100 vitiligo patients with an age range between 18 to 60 years and 100 controls with matched age, gender, and body mass index. All subjects were tested for MS components. Serum visceral adipose tissue-derived serine protease inhibitor (vaspin), fatty acid binding protein 4 (FABP4), vascular adhesion protein 1 (VAP-1), chitinase-3-like protein 1 (YKL-40), and high-sensitivity C-reactive protein (hs-CRP) were also measured. Results: Regarding MS, it was observed in 22.0% of vitiligo patients and 2.0% of control subjects (P < 0.001). Serum FABP4, VAP-1, YKL-40, and hs-CRP concentrations were higher in patients than in the control group (P < 0.05 each), and their levels showed high sensitivity and specificity to differentiate MS when using the receiver operating characteristic (ROC). Levels of these markers, except serum vaspin, were significantly positively correlated with lipid profile markers (except high-density lipoprotein cholesterol) and fasting blood glucose levels (P < 0.05 each). Conclusion: MS was more common in vitiligo patients. The levels of the biomarkers studied were significantly higher in vitiligo patients. Furthermore, their levels accurately predicted MS in vitiligo patients. According to current research, these markers may be useful in assessing MS risk in vitiligo patients. Extensive research, however, is required.

Apolipoprotein E Gene Polymorphism, Serum Lipids, and Risk of Superficial Fungal Infections in Egyptian Patients - A Preliminary Case-Controlled Study.

Background: Apolipoprotein E (APOE) gene isoforms have been found to affect the risk of superficial fungal infections (SFIs). However, the data only cover a few ethnicities. Aims: The present work intended to investigate the association of APOE gene polymorphism and serum lipids with the susceptibility of SFIs among a group of Egyptian patients. Materials and Methods: Standard laboratory methods were used to estimate the serum lipid profile, and polymerase chain reaction-restriction fragment length polymorphism was used to detect APOE gene polymorphism in deoxyribonucleic acid extracted from 150 SFI patients and an equal number of apparently healthy matched controls. Results: Serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol were significantly higher in the studied patients than in controls. The APOE gene ε2, ε4 alleles, and ε3/4 and ε3/2 genotypes were significantly distributed in the patients than in the controls. APOE ε3/3 genotype was predominant in dermatophytosis and tinea versicolour patients, and ε3/4 genotype was predominant in candidiasis. Conclusions: ApoE alleles ε2 and ε4, and genotypes ε2/3 and ε3/4 are linked to SFI and may be risk factors, whereas allele ε3 and genotype ε3/3 may be protective for SFI in the Egyptian population studied. The lipid profile results suggest that hyperlipidemia may provide evidence for SFI pathogenesis. However; further large-scale studies are still needed to validate our results.

Toxoplasma gondii Suppresses Th2-Induced by Trichinella spiralis Infection and Downregulates Serine Protease Genes Expression: A Critical Role in Vaccine Development.

Background: Toxoplasma gondii coinfection can modify host immune responses and the severity and spread of other parasites. We investigated how T. gondii and Trichinella spiralis infections counter-regulate each other's immune responses. Methods: The parasite burden, the expression of T. gondii rhoptry kinase ROP18 and T. spiralis putative serine protease (TsSP), the IgG1 and IgG2a responses, besides histopathological and immunohistochemical staining with iNOS and arginase were used to evaluate the dynamics of coinfection. Results: Through their effects on host immune responsiveness, coinfection with T. gondii modified the virulence of T. spiralis infection. Coinfected animals with high and low doses of T. gondii demonstrated significant reductions in the T. spiralis burden of 75.2% and 68.2%, respectively. TsSP expression was downregulated in both groups by 96.2% and 86.7%, whereasROP18 expression was downregulated by only 6% and10.6%, respectively. In coinfected mice, elevated levels of T. gondii-specific IgG2a antibodies were detected. Th1 induced by T. gondii inhibits the Th2 response to T. spiralis in coinfected animals with high iNOS expression andlow-arginine1 expression. Conclusion: T. gondii infection induces a shift toward a Th1-type immune response while suppressing a helminth-specific Th2 immune response, paving the way for developing novel vaccines and more efficient control strategies.

Serum Soluble Intercellular Adhesion Molecule-1 (sICAM-1): A Novel Potential Biomarker in Severe Acne Vulgaris.

Background: Acne vulgaris (AV) is a chronic inflammatory disorder. Intercellular adhesion molecule-1 (ICAM-1) is a vital adhesion molecule mediating cellular adhesion during the inflammatory process. Aims and Objectives: To evaluate serum soluble intercellular adhesion molecule-1 (sICAM-1) level in AV patients as an attempt to elucidate its role in acne pathogenesis and to relate with studied clinical parameters. Materials and Methods: Serum sICAM-1 level was measured using ELISA technique in 60 patients and 60 controls. Results: Serum sICAM-1 level was significantly elevated in studied patients than controls (P < 0.001). Additionally, its level increased significantly with increased acne severity (P < 0.001) but not in patients with post acne scars (P > 0.05). Conclusion: Serum sICAM-1 could be a marker for acne etiopathogenesis. Furthermore, it might be considered as a predictor for disease severity.

Diagnostic implications of MicroRNAs; 155, 146 a, and 203 lesional expression in alopecia areata: A preliminary case-controlled study.

BACKGROUND: Alopecia areata (AA) is an immune mediated disorder that attacks hair follicles with unknown pathophysiology. MicroRNAs (miRNAs) are small noncoding RNA molecules, and their aberrant expression or function has been involved in different autoimmune conditions. OBJECTIVES: We aimed at exploring the association between some miRNAs lesional expression and AA pathogenesis by measurement of miRNAs-155, 146a, and 203 expression levels in the lesional skin from patchy AA patients and to evaluate their relation with the studied parameters. SUBJECTS AND METHODS: Skin expression levels of miRNAs-155, 146a, and 203 were evaluated in 50 patients with patchy AA and 25 healthy controls using reverse transcriptase-quantitative PCR (RT-qPCR). The activity and severity of alopecia were assessed according to AA Investigational Assessment Guidelines criteria. RESULTS: Studied patients showed significant up-regulation of miRNAs-203, 146a, and 155 lesional tissue expression levels when compared to control group (p < 0.05 each). Only miRNA-146a skin expression level was significantly higher in patients with multiple lesions (p < 0.001). However, patients with active AA had significantly higher tissue expression levels of the investigated miRNAs than those with inactive disease (P 0.001, 0.009, and 0.001, respectively). CONCLUSIONS: Investigated miRNAs seem to be role players in AA pathogenesis and may be considered potential indicators of disease activity. However, more research is needed to clarify their accurate role and clinical importance.

Serum Fetuin-A: A Novel Potential Link Between Post-adolescent Acne and Insulin Resistance.

Background: Post-adolescent acne is acne in patients aged older than 25 years. It is more common in women, suggesting an underlying hormonal imbalance. It has been postulated that insulin resistance (IR) may play a role in pathogenesis. Objective: To explore the relationship between fetuin-A, IR, and post-adolescent acne. Methods: Serum fetuin-A levels were assessed using an ELISA technique in 50 female patients with post-adolescent acne and 50 healthy controls, and IR was calculated using the Homeostasis Model Assessment of Insulin Resistance Index (HOMA-IR). Results: Studied patients had significantly higher HOMA-IR indices and serum fetuin-A levels than control subjects (P=0.001 and <0.001, respectively) and they were significantly increased in patients with severe lesions (P<0.001). Conclusion: We found that IR was more significantly prevalent among studied patients, especially those with more severe acne grades, and that could be attributed to higher serum fetuin-A levels. Fetuin -A might be a predictor for acne severity and associated metabolic comorbid conditions, such as IR. However, further large-scale studies will be needed.

Association between angiotensin-converting enzyme gene insertion deletion polymorphism and androgenetic alopecia susceptibility among Egyptian patients: A preliminary case-controlled study.

BACKGROUND: Androgenetic alopecia (AGA) is a prevalent condition with a complex etiopathogenesis. Angiotensin-converting enzyme (ACE) gene located on the chromosome 17q23 contains an insertion (I) and deletion (D) polymorphism in the intron 16. This gene polymorphism plays a role in multiple inflammatory disorders. However, there are no studies investigating its association with AGA susceptibility. OBJECTIVES: In this work, we aimed at exploring the association of ACE gene I/D polymorphism in AGA susceptibility in a group of Egyptian patients. METHODS: This study included 100 AGA patients, and 100 apparently healthy controls. The ACE gene I/D polymorphism was analyzed by polymerase chain reaction. RESULTS: The DD, ID genotypes, and D allele showed higher frequent distribution among studied AGA patients than controls (p < 0.05 each). Positive family history and ACE gene I/D polymorphism were considered AGA susceptibility predictors in both uni- and multivariable analyses [p < 0.05 each (OR (95% CI)] on applying logistic regression analysis for risk factors prediction. CONCLUSIONS: This study highlights the possible contribution of the suspected genetic polymorphism as a susceptibility indicator for AGA development in the examined group of patients.

Mitigation of Toxoplasma gondii-induced ileitis by Trichinellaspiralis infection pinpointing immunomodulation.

The current study sought to investigate the potential role of Trichinellaspiralis infection in the treatment of T. gondii-induced ileitis. Forty male Swiss albino mice were divided into four groups:a normal control group Igiven only phosphate-buffered saline (PBS), Group II givenPBS for 28 days then infected with T. gondii cysts for the induction of gastroenteritis, Group III infected only with T. spiralis larvae, and Group IV concurrently infected with T. spiralis larvae, then 28 days post infection, enteritis was induced by oral inoculation withT. gondii cysts. Histopathologicaland immunohistochemicalassessmentswere performed to determine the levels of inflammatory markers nuclear factor- κB (NF-κB) and myeloperoxidase in the ileum samples.Theconcentrations of cytokinesIFN-γ and IL10 were measured in successive serum samples. Histological assessment revealed severe inflammatory infiltrations in ileum samples of T. gondiimonoinfected mice. In addition, the immunological assessment revealed elevated levels of IFN-γ and decreased IL10 concentrations in blood samples. Clear improvement of inflammations, besidesthe decreasedlevels of IFN-γ and increased IL10 concentrations in blood samples were detected in T. spiraliscoinfected animals.Theileal tissue revealed elevated expression of (NF-κB) and myeloperoxidase signaling, all of which were mitigated by T. spiralis coinfection. There is a possibility that regulatory T cells are immunomodulated, releasing anti-inflammatory cytokines while suppressing pro-inflammatory cytokines, causing its therapeutic impact. Trichinellaspiralis infection has the potential to be used for treatment of T. gondii-induced ileitis. As a consequence of these encouraging results, T. spiralis crude and secretory-excretory antigens coated on nanoparticles are being studied in our future research.

Cross talk between oxidative stress and inflammation in alopecia areata.

BACKGROUND: Although the etiopathogenesis of alopecia areata (AA) is still unclear, inflammation, oxidative stress, and subsequent DNA damage might be considered role players in disease development. AIM: We aimed at exploring the potential link between oxidative DNA damage and inflammation in AA patients through measuring 8-hydroxy deoxyguanosine (8-OHdG), high mobility group box 1 protein (HMGB1), and one of the inflammatory mediators, C-reactive protein (CRP). METHODS: A total of 79 subjects (49 AA patients in addition to 30 apparently healthy control subjects) were tested for serum levels of 8-OHdG, HMBG1, and CRP. RESULTS: Compared with the control group, serum 8-OHdG, HMBG1, and CRP levels were significantly elevated in the studied patients group (0.031, <0.001, and <0.001, respectively). Moreover, logistic regression analysis revealed that disease course, serum levels of 8-OHdG, and HMBG1 were considered independent predictors for AA severity in both uni- and multivariable analyses. CONCLUSION: Our results suggest a possible role of oxidative stress together with proinflammatory biomarkers in development of AA and their benefit in predicting a severe form of the disease.

The delayed death-causing nature of Rosmarinus officinalis leaf extracts and their mixture within experimental chronic toxoplasmosis: Therapeutic and prophylactic implications.

BACKGROUND: The restricted effect, significant toxicity, and emerging resistance of anti-toxoplasmosis synthetic agents impose the search for alternatives. The current research aimed to evaluate the prophylactic and therapeutic efficacy of Rosmarinus officinalis extracts and their mixtures against chronic murine toxoplasmosis and to clarify the phenomenon of delayed death. METHODS: This research included two experimental designs, the first to test the preventive and curative efficacy of the extracts and the second to assess delayed death in mice infected with the ME49 strain of Toxoplasma gondii. The essential oils of the plant were analyzed by gas chromatography/mass spectrometry. RESULTS: Treatment with a mixture of rosemary extracts displayed reduction rates of 81% for T. gondii cyst burden and 23% for cyst viability. The reinfected group with the pretreated cysts reported 93.4% reduction in cyst burden and 95.4% in cyst viability. Moreover, 90% reduction of the infectivity rate was obtained. The therapeutic efficacy of this mixture was superior to its valuable prophylactic effect. Histopathological examination of liver and brain tissue exhibited marked improvement. Both extracts possess free radical scavenging and antioxidant activities evidenced by high expression of iNOS stain. Our results were signified by low BAG-1 gene expression and massive mutilation of T. gondii cyst in the targeted group using scanning electron microscopy. Analysis of R. officinalis revealed the presence of isobornylformate as a novel ingredient. CONCLUSIONS: R. officinalis displays a therapeutic rather than prophylactic potential, indicating the emergence of an effective safe alternative therapy.

Evaluation of the effect of some medicinal plants on cultured Trichomonas Vaginalis.

INTRODUCTION: Trichomoniasis is a worldwide sexually transmitted disease caused by Trichomonas vaginalis. It inflicts severe complications to the human genitourinary system. The devastating negative effects and the emergence of resistance to common medication impose the search for safer and effective alternatives. This research aimed to investigate the effect of the Allium sativum, Nigella sativa crude extracts (NsCE) and the combination between their most effective doses with metronidazole. METHODOLOGY: Vaginal swabs were obtained from symptomatic patients, and cultured on Diamond's medium. Assessment of various concentrations of these herbs at different follow-up periods was done by counting the number of dead T. vaginalis trophozoites using the hemocytometer and trypan blue staining. Transmission electron microscope study was done. RESULTS: NsCE 9 mg/mL yielded the highest lethal effect on T. vaginalis trophozoites after 72 hours, compared with metronidazole. Combination of NsCE 9 mg/mL and metronidazole 50 µg/mL gave the best result. Additionally, Tomex90 µg/mL, represents a tolerable effect after 72 hours, but metronidazole 100 µg/mL still has higher effect. These results were confirmed by the ultrastructural changes observed in T. vaginalis trophozoites, signifying severe damage of nucleus and cytoplasm with large vacuolization and cell membrane defects. CONCLUSIONS: NsCE is a promising anti-Trichomonas especially its combination with metronidazole which showed a high synergistic effect.

Angiotensin-converting enzyme gene insertion/deletion polymorphism and family history in severe acne vulgaris.

BACKGROUND: Acne vulgaris is an inflammatory disorder with a profound heterogenous aetio-pathophysiology. ACE gene I/D polymorphism affects angiotensin-converting enzyme activities that play a role in inflammation. However, there are no molecular genetic studies investigating the contribution of ACE gene insertion/deletion polymorphism in the genetic background of acne vulgaris. AIMS: The aim of this work was to reveal the relation between the ACE gene I/D polymorphism and acne vulgaris development among a sample of patients. PATIENTS AND METHODS: This study included 100 acne vulgaris patients in addition to 120 matched control subjects. The ACE gene I/D polymorphism was analyzed using polymerase chain reaction (PCR). RESULTS: The distribution of DD, ID genotypes, and D allele showed higher frequency in AV patients than in controls (P < 0.001 for all). Moreover, positive family history and ACEI/D gene polymorphism (DD + ID genotypes) were considered as independent predictors for severe acne grades (P ≤ 0.001 and 0.046, respectively) in multivariate analysis. CONCLUSIONS: The current study results suggest that the D allele of the ACE I/D gene polymorphism might confer risk to AV among the studied patients. Moreover, ACE I/D gene polymorphism and positive family history were considered as independent predictors of severe AV.

Effect of Nitazoxanide, Artesunate Loaded Polymeric Nano Fiber and Their Combination on Experimental Cryptosporidiosis.

BACKGROUND: Cryptosporidium parvum is a dangerous intestinal pathogen due to its devastating effect on immunocompromised individuals. Considering low efficacy, high toxicity in addition to the development of resistance for the drugs used, this study aimed to find a new alternative treatment having the advantage of lower doses and minimal toxicity. We used a novel combination between artesunate loaded polymeric nanofiber (ALPN) and nanazoxide that had not been tried yet. METHODS: Sixty Swiss Albino mice aged 6-7 wk, weighting 20-24 gm were used in Theodor Bilharz Research Institute (TBRI) Cairo, Egypt in 2017. C. parvum oocysts collected from patients were identified by polymerase chain reaction to be used for infecting animals. The effect of combination between ALPN and nana-zoxide were assessed by oocyst count in stool of experimental animals using modified Ziehl-Neelsen stain and histopathological changes in intestinal tissue. Antioxidant activity of nanofiber-loaded artesunate was estimated in serum, renal, hepatic and intestinal tissues by demonstrating the reactive oxygen species and the total antioxidant capacity. It was confirmed by detection of inducible nitric oxide synthase (iNOS) antibody. RESULTS: The novel combination between ALPN and nanazoxidehas a harmonizing effect in reducing oocyst shedding (94.4%), the mean value of the antioxidant levels in liver, intestine, kidney, and serum were the highest level (10.15, 22.4, 6.22, 14.08 respectively) resulting in the decrease of oxidative stress in tissues. Marked improvement of histopathological features was obtained. CONCLUSION: This combination has a promising therapeutic effect against cryptosporidiosis particularly in immunocompromised individuals considering minor toxicity.

Knowledge of Neonatal Hyperbilirubinemia Among Primary Health Care Physicians: A Single-Center Experience.

BACKGROUND AND OBJECTIVES: To evaluate the knowledge of the primary health care physicians (PHCP) in Kalubia governorate, Egypt, about the causes, diagnosis, complications, and treatment of neonatal hyperbilirubinemia (NHB). METHODS: Cross-sectional survey distributed by interview to 500 physicians working in the primary health care (PHC) sector in Kalubia. RESULTS: Out of 500 distributed surveys, 419 (84%) PHCP completed the questionnaire. They represent 174 (90%) out of 193 PHC units and centers. About 18% were males and 82% females with mean age of 28.5 ± 5.2 years, and mean duration of work was 3.3 ± 4.4 years. All of the respondents have patients with NHB in their daily practice. The knowledge of the PHCP was good in some aspects about NHB; however, it was poor and may be even hazardous in other aspects. CONCLUSIONS: Many areas of defects are detected in PHCP knowledge about NHB. Pre-service and continuous training of the PHCP about the diagnosis and management of NHB are essential.

Perturbed adipose tissue hydrogen peroxide metabolism in centrally obese men: Association with insulin resistance.

OBJECTIVE: Although adipose tissue hydrogen peroxide (H2O2) and its metabolizing enzymes have been linked to obesity and insulin resistance in animal studies, this relation remains to be evaluated in humans. METHODS: Non-diabetic men (N = 43, median age, 49 (37, 54 y)) undergoing abdominal surgeries were studied. Participants were classified by body mass index (BMI) into normal-weight (N = 19), or overweight/obese (Ow/Ob; BMI ≥25; N = 24). Centrally obese men were identified by waist-height ratio ≥0.5. H2O2 and activities of superoxide dismutase, catalase and glutathione peroxidase enzymes were assayed in subcutaneous fat samples, and visceral fat (available from N = 33), and their associations with anthropometric parameters, fasting serum lipids, and the homeostasis model of insulin resistance (HOMA-IR) were tested using correlations and multivariate linear regression. RESULTS: H2O2 concentrations and catalase activity were increased in visceral fat from Ow/Ob men, compared to normal-weight subjects (+32%, P = 0.038 and +51%, P = 0.043 respectively). Centrally obese subjects had >2-fold higher superoxide dismutase activity (P = 0.005), 46% higher H2O2 (P = 0.028), and 89% higher catalase activity (P = 0.009) in visceral fat, compared to lean subjects. Central obesity did not alter these markers in subcutaneous fat, apart from a 50% increase in catalase, and did not affect glutathione peroxidase in either fat depot. H2O2 in visceral fat positively correlated with insulin resistance (r = 0.40, P = 0.032). Catalase activity in visceral fat was an independent determinant of HOMA-IR, explaining ~18% of the variance (ß = 0.42, P = 0.016), after adjustment for age and BMI. CONCLUSION: These findings suggest that adipose tissue catalase shows compensatory up-regulation in response to obesity-induced H2O2 accumulation, and that perturbed H2O2 metabolism in visceral fat is linked to insulin resistance in obese humans.