Testicular veins: anatomy and role in varicocelogenesis and other pathologic conditions

The anatomy of the testicular veins of 42 male cadavers were studied to determine the extent of their role in varicocelogenesis and other pathologic conditions. The results of that study are presented.     

Granulocyte‐macrophage colony‐stimulating factor,a potent adjuvant for polarization to Th‐17 pattern: an experience on HIV‐1 vaccine model

Cytokines are mediators for polarization of immune response in vaccines. Studies show that co‐immunization of DNA vaccines with granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) can increase immune responses. Here, experimental mice were immunized with HIV‐1_{tat/pol/gag/env} DNA vaccine with GM‐CSF and boosted with recombinant vaccine. Lymphocyte proliferation with Brdu and CTL activity, IL‐4, IFN‐γ, IL‐17 cytokines, total antibody, and IgG1 and IgG2a isotypes were assessed with ELISA. Results show that GM‐CSF as adjuvant in DNA immunization significantly increased lymphocyte proliferation and IFN‐γ cytokines, but CTL response was tiny increased. Also GM‐CSF as adjuvant decreased IL‐4 cytokine vs mere vaccine group. IL‐17 in the group that immunized with mixture of DNA vaccine/GM‐CSF was significantly increased vs DNA vaccine group. Result of total antibody shows that GM‐CSF increased antibody response in which both IgG1 and IgG2a increased. Overall, results confirmed the beneficial effect of GM‐CSF as adjuvant to increase vaccine immunogenicity. The hallmark result of this study was to increase IL‐17 cytokine with DNA vaccine/GM‐CSF immunized group. This study for the first time provides the evidence of the potency of GM‐CSF in the induction of IL‐17 in response to a vaccine, which is important for control of infection such as HIV‐1.     

Expression of Leptin and Visfatin in Gingival Tissues of Chronic Periodontitis With and Without Type 2 Diabetes Mellitus: A Study Using Enzyme‐Linked Immunosorbent Assay and Real‐Time Polymerase Chain Reaction

Background: The aim of this study is to investigate the protein and gene expression of leptin and visfatin in gingival tissue from patients with chronic periodontitis (CP), patients with CP and type 2 diabetes mellitus (T2DM), and healthy individuals. Methods: The study includes 50 individuals: 10 healthy individuals, 20 patients with CP, and 20 patients with CP and T2DM. Plaque index, gingival index, probing depth, and clinical attachment loss were measured, and gingival biopsies were obtained. Leptin and visfatin protein expression in gingival tissues was determined using enzyme‐linked immunosorbent assay, and messenger RNA (mRNA) expression was measured via real‐time polymerase chain reaction. Results: The highest leptin mRNA and protein expression was observed in the control group and was significantly (P ≤0.05) different from the CP and CP+T2DM groups. Gingival tissues from patients with CP and T2DM had a significant increase in visfatin and a decrease in leptin gene and protein expression (P <0.05) compared with both controls and patients with CP. Conclusion: Expression of leptin and visfatin in the gingival tissues suggests a possible role for these adipokines in the pathogenesis of CP and T2DM.     

Modulation of JNK-1/ β-catenin signaling by Lactobacillus casei,inulin and their combination in 1,2-dimethylhydrazine-induced colon cancer in mice

Colon cancer is a complex disease that involves numerous genetic alterations that change the normal colonic mucosa into invasive adenocarcinoma. In the current study, the protective effects of inulin (prebiotic), Lactobacillus casei (L. casei, probiotic) and their combination (synbiotic) on 1,2-dimethylhydrazine (DMH)-induced colon cancer in male Swiss mice were evaluated. Animals were divided into: Control group, DMH-treated group, DMH plus inulin, DMH plus L. casei and DMH plus inulin plus L. casei-treated groups. Fecal microbiome analysis, biochemical measurements, histopathological examination of the colon tissues, immunostaining and Western blotting analysis of β-catenin, GSK3β and JNK-1 were performed. The prebiotic-, probiotic- and synbiotic-treated groups showed decreased levels of carcinoembryonic antigen and a lower number of aberrant crypt foci compared to the DMH-treated group with the synbiotic group exhibiting a superior effect. Furthermore, all treatments showed a body weight-reducing effect. Administration of inulin, L. casei or their combination increased the expression level of phospho-JNK-1 while they decreased the expression level of β-catenin and phospho-GSK3β. Remarkably, L. casei treatment resulted in enrichment of certain beneficial bacterial genera i.e. Akkermansia and Turicibacter. Therefore, administration of L. casei and inulin as a synbiotic combination protects against colon cancer in mice.

The lactobacillus casei and inulin modulate the expression of JNK-1, GSK3β and β-catenin proteins and enrich the beneficial bacteria to protect from colon cancer in mice.     

Excellent outcome of allogeneic bone marrow transplantation for Fanconi anemia using fludarabine-based reduced-intensity conditioning regimen

Fanconi anemia (FA) is a disorder characterized by developmental anomalies, bone marrow failure and a predisposition to malignancy. It has recently been shown that hematopoietic stem cell transplantation using fludarabine (FLU)-based reduced-intensity conditioning is an efficient and quite safe therapeutic modality. We retrospectively analyzed the outcome of bone marrow transplantation (BMT) in eight patients with FA performed in two institutes between 2001 and 2011. There were seven females and one male with a median age at diagnosis = 4.5 years (range 2-12 years). The constitutional characteristics associated with FA, such as developmental anomalies, short stature and skin pigmentation, were absent in three of the patients. One patient showed myelodysplastic features at the time of BMT. All patients received BMT using FLU, cyclophosphamide (CY) and rabbit anti-thymocyte globulin (ATG) either from a related donor (n = 4) or an unrelated donor (n = 4). Acute graft-versus-host disease (GVHD) of grade I developed in one patient, while chronic GVHD was not observed in any patient. All patients are alive and achieved hematopoietic recovery at a median follow-up of 72 months (range 4-117 months). BMT using FLU/low-dose CY/ATG -based regimens regardless to the donor is a beneficial therapeutic approach for FA patients.     

Study of the Rectal Electric Activity of the Uninhibited Rectal Detrusor (Overactive Rectum): A New Concept of Pathogenesis

Abstract

Background/Objective: One of the causes of fecal incontinence is uninhibited rectal detrusor syndrome (URDS). Patients with this condition either perceived the first rectal sensation after the onset of involuntary rectal contraction or not at all. We investigated the hypothesis that the abnormal rectal contractility in URDS may be caused by deranged rectal electric activity.

Methods: Twenty-five patients with URD (14 women and 11 men; age, 44.7 ± 10.3 years) and 10 healthy volunteers (6 women and 4 men; age, 42.8 ± 8.7 years) were studied. URDS was diagnosed by rectometry and provocative test. A transcutaneous EMG was performed with one electrode placed lateral to each sacroiliac joint and the third one midway between the greater trochanter and the ischial tuberosity. Two 20- minute recording sessions were performed for each subject.

Results: Slow waves (SWs) with regular rhythm and similar parameters (frequency, amplitude, conduction velocity) from the 3 electrodes were recorded from the healthy volunteers. They showed a significant increase in the parameters on saline filling of the rectum. The SWs of patients with URDS exhibited a “dysrhythmic” pattern with irregular parameters, which were different in the 3 electrodes and inconsistent during recording. They showed areas of tachyrhythmia, bradyrhythmia, and arrhythmia. On provoking rectal overactivity, the SWs showed an increased dysrhythmic activity.

Conclusions: The patients with URD exhibited a “dysrhythmic” electric pattern with areas of variable electric activity. The tachyrhythmic areas seem to initiate the urgency and fecal incontinence of URDS. It is suggested that a disordered rectosigmoid pacemaker causes the dysrhythmic waves.     

Effect of Perineal Compression on the Rectal Tone

PURPOSE: Digital pressure on the perineum was reported to result in an increase of the rectal tone. This effect has been related to a reflex action named perineorectal reflex but was not verified. The mechanism of action of perineal pressure on the rectal tone was studied. METHODS: Eighteen healthy volunteers (mean age +/- standard deviation, 39.7 +/- 11.8 years; 10 males) were studied. The barostat system used consisted of a polyethylene balloon connected to a strain gauge and a computer-controlled, air-injection system. The balloon was introduced into the rectum, and the rectal tone was assessed by recording the balloon volume variations in response to digital pressure on the perineum. The test was repeated after individual anesthetization of perineum and rectum. It was performed again using normal saline instead of Xylocaine. RESULTS: During perineal pressure, all the volunteers exhibited rectal tone increase with a mean decrease in the balloon volume of 72.3 +/- 14.7 percent. There was no significant difference (P > 0.05) in the rectal tone response between females and males nor between young and elderly patients. The mean latency was 17.3 +/- 1.8 ms. Perineal pressure 20 minutes after individual anesthetization of perineum and rectum effected no significant rectal tone changes. The response returned after the anesthetic effect had waned. The rectal tone response after saline administration was similar to that before administration. CONCLUSION: The study has shown that rectal tone increase during digital perineal pressure represents most probably a reflex action. This was evidenced by absence of rectal tone response on individual anesthetization of the assumed two arms of the reflex arc: perineum and rectum. The perineorectal reflex may be of diagnostic significance in rectal motor disorders and has the potential to be used as an investigative tool, provided further studies are performed to prove these points.     

On the mechanism of colonic motility: the electric activation theory of colonic contraction

PURPOSE: A previous study has demonstrated that the longitudinal muscle possesses electric activity, while the circular does not (A. Shafik and A. A. Shafik, 2000, Front. Biosci. 5, b5). In the current study, we investigated the mechanism of action of the two colonic muscle coats in the motility of the gut. METHODS: Fourteen patients (43.8 years, 10 men) with left colon or rectal cancer were scheduled to have transverse colostomy as a part of their operation. The electric activity of the ascending colon was recorded by three electrodes applied to each of the circular and the longitudinal (taenia coli) muscle coats. Simultaneously, the colonic pressure was recorded before and after colonic distension. The test was repeated after longitudinal muscle anesthetization. RESULTS: Electric waves in the form of pacesetter (PPs) and action (APs) potentials were recorded from the longitudinal but not the circular muscle fibers. APs were associated with an intracolonic pressure rise. Colonic distension produced significant increase in the PPs and APs recorded from the longitudinal muscle with appearance of similar electric activity from the circular muscle. Electric activity and colonic pressure increased upon increase in the colonic distension until the balloon in the proximal part of the ascending colon moved to the transverse colon in one mass contraction. Ten minutes after longitudinal muscle anesthetization, no electric activity was recorded from the longitudinal and circular muscles upon colonic distension. CONCLUSIONS: The electric waves appear to be transmitted from the longitudinal to the circular muscle upon colonic distension. The giant migrating contractions of the colon that move the food bolus from the cecum to the transverse colon are suggested to be a function of the longitudinal muscle electric activation with gut lumen modulation by the circular fibers.