Dual Strategy with Adipose-Derived Stem Cells and l-arginine Recovered Cavernosal Functions in a Rat Model of Radical Prostatectomy.

As standard therapy for prostate cancer, radical prostatectomy causes cavernous nerve (CN) injury and increases fibrosis and hypoxia-induced penile structural alterations. This study aimed to determine the potential beneficial effects of adipose-derived stem cells (ADSCs) and l-arginine alone or in combination on the penile erection in a rat model of erectile dysfunction caused by bilateral cavernous nerve transection (CNT). Male rats (n = 35) were randomized into five groups: Sham-operated; CNT (4-weeks); CNT plus ADSCs (1 × 106 cells by intracavernosal injection); CNT plus l-arginine (4 weeks, 10 mg/kg/day, oral); and ADSCs combined with l-arginine in CNT. In vivo erectile responses and in vitro relaxant responses were measured. Western blot and immunohistochemistry analyses were used to determine the expression and localization of endothelial nitric oxide synthase, neuronal nitric oxide synthase, transforming growth factor-beta 1, hypoxia-inducible factor-1 alpha (HIF-1α), and apoptosis markers (Bax and Bcl-2). The ratio of smooth muscle to collagen and nerve regeneration were calculated using Masson's trichrome and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining. The combined treatment restored diminished erectile responses, endothelium-dependent acetylcholine, and electrical field stimulation-induced relaxation of the corpus cavernosum in rats with CNT, whereas either monotherapy produced only partial improvements. All treatment regimens restored increases in the protein expression of HIF-1 and Bax in rats with CNT. The decrease in smooth muscle mass and NADPH-diaphorase-positive nerve fibers was partially ameliorated by monotherapy, whereas combined therapy led to recovery. These findings indicate that combined treatment with ADSCs and l-arginine may restore erectile function in rats with CNT by inhibiting hypoxia-induced neurotoxicity and preserving endothelium function and smooth muscle content.

Clinicopathological Assesment in Patients with Enterobius vermicularis Infection

OBJECTIVE: Enterobius vermicularis is a common gastrointestinal parasite. Acute appendicitis is one of the most common clinical conditions requiring surgical intervention. The coexistence of enterobiasis and acute appendicitis has attracted the attention of researchers for a long time. In this article, it is aimed to present the characteristics of enterobiasis cases detected in appendectomy specimens in a tertiary healthcare institution. In addition, it is aimed to reveal the differences by comparing the cases diagnosed with acute appendicitis without enterobiasis. METHODS: All cases operated for acute appendicitis between January 1, 2008 and December 31, 2021 were retrospectively evaluated through the hospital registry system. The cases with histopathologically determined E. vermicularis were reviewed and a study group was formed. The control group consisted of patients diagnosed with acute appendicitis for reasons other than enterobiasis, matched with the study group in terms of age and gender. Complete blood count, C-reactive protein (CRP) ultrasonography evaluations were compared between the two groups. RESULTS: During the study period, 3.650 appendectomy materials were examined; E. vermicularis was detected in 1.32% (n=48) cases, and acute appendicitis was present in 33.33% (n=16) of the cases. Lymphoid hyperplasia was the most common histopathological change in the study group (n=25; 52.08%). When compared to the control group, leukocyte, neutrophil, CRP, ultrasonographic appendix diameter values were found to be significantly higher in the control group, and the percentage of eosinophils in the study group (p<0.0001; p<0.0001; p<0.0001; p<0.0001; p=0.001; respectively). CONCLUSION: Enterobiasis is a common parasite especially in children. Rarely, it can be seen in patients with acute appendicitis. Histopathological evaluation is necessary to ensure a safe surgical procedure and to complete the treatment with anthelmintic drugs. Enterobiasis should be kept in mind in cases when the acute phase response is lower than expected.

Sodium butyrate ameliorates erectile dysfunction through fibrosis in a rat model of partial bladder outlet obstruction.

BACKGROUND: In different animal models, a histone deacetylase (HDAC) inhibitor, sodium butyrate (NaBu) reduced inflammation, oxidative stress and fibrosis which were involved in the pathogenesis of erectile dysfunction (ED), but whether NaBu could improve ED in an experimental animal model of benign prostate hyperplasia (BPH) was not known. OBJECTIVE: To investigate the preventive effect of NaBu on ED in a partial bladder outlet obstruction (PBOO) rat model. MATERIALS AND METHODS: PBOO was induced by partial urethral obstruction. NaBu (20 mg/kg/day) was administered orally to rats for 6 weeks after creation of PBOO. In vivo erectile responses, in vitro relaxation and contraction responses in cavernosal tissue were measured. Real-time polymerase chain reaction (RT-PCR) and Western blot were performed to determine the gene and protein expression. Inflammation, fibrosis, and localization of proteins were evaluated using histological techniques. HDAC activity and tumor necrosis factor (TNF)-α levels were measured in penile tissues. RESULTS: NaBu improved decreased intracavernosal pressure/mean arterial pressure, nitrergic and endothelium-dependent relaxation responses, and contractile responses to phenylephrine and electrical field stimulation in the PBOO group without affecting increased bladder weight. Increased endothelial nitric oxide synthase (eNOS), transforming growth factor (TGF)-ß1, and nuclear factor kappa B (NF-κB) gene levels in PBOO group were ameliorated by NaBu treatment. The administration of NaBu to PBOO rats significantly increased neuronal NOS (nNOS) and decreased TGF-ß1 protein expression. The nuclear/cytosolic ratio of NF-κB demonstrated a decrease in PBOO and all treatment groups compared to control. A significant increase in the nuclear-to-cytoplasmic ratio of nuclear factor erythroid 2-related factor 2 (Nrf2) after PBOO was reduced by the treatment. Both eNOS and inducible NOS (iNOS) protein expression, together with TNF-α levels did not differ in the penile tissue of all groups. In histological analysis, increased TGF-ß1 protein expression and fibrosis, as well as decreased nNOS protein in PBOO, were reversed by the treatment. NaBu did not normalize moderate inflammation in obstructed rats. An increase in the HDAC activity in PBOO was significantly suppressed by NaBu. DISCUSSION: Inhibition of the HDAC activity by NaBu in penile tissue could ameliorate fibrosis-associated changes induced by PBOO. CONCLUSION: NaBu promotes recovery of erectile function, and also significantly prevents penile fibrosis and normalizes TGF-ß1 and nNOS protein expression in a rat model of PBOO. The HDAC pathway may present a promising target to prevent ED in patients with BPH.

Beneficial Effects of Human Umbilical Cord Blood Mononuclear Cells on Persistent Erectile Dysfunction After Treatment of 5-Alpha Reductase Inhibitor in Rats.

BACKGROUND: Effects of human umbilical cord blood (HUCB) as a valuable source for stem cell-based therapies have not been studied in persistent post-5-alpha reductase inhibitors (5ARI) erectile dysfunction (PPED). AIM: To determine the effect of intracavernosal injection of HUCB mononuclear cells (MNCs) on ED associated with dutasteride treatment. METHODS: Twenty five adult male Sprague-Dawley rats were divided into 5 groups (n = 5 per group): (i) control, (ii) 8-week dutasteride (0.5 mg/kg/day, in drinking water), (iii) 12-week dutasteride, (iv) 8-week dutasteride+HUCB-MNCs (1 × 106) and (v) 12-week dutasteride+HUCB-MNCs. HUCB-MNCs were administered intracavernosally after eight weeks of dutasteride treatment. Experiments were performed at 4 weeks following the injection of HUCB-MNCs. Erectile responses and isometric tension of corpus cavernosum (CC) were measured. The protein expressions of phosphodiesterase type 5 (PDE5), endothelial nitric oxide synthase (eNOS), neuronal NOS (nNOS), hypoxia-inducible factor (HIF)-1α and smooth muscle/collagen contents in penile tissue were evaluated by Western blotting, immunohistochemistry, and Masson's trichrome staining, respectively. MAIN OUTCOME: In vivo erectile function, in vitro relaxant and contractile responses of CC, protein expression and localization of PDE5, eNOS, nNOS, HIF-1α, and smooth muscle content in penile tissue. RESULTS: Erectile responses in the dutasteride-treated groups were significantly decreased compared with controls (P < .001), persisting after 4-wk of washout. HUCB-MNCs restored diminished intracavernosal pressure responses, acetylcholine-, sodium nitroprusside-, sildenafil-induced relaxations, and increased phenylephrine and electrical field stimulation (EFS)-induced contractions. Decreased EFS-induced relaxations in dutasteride-treated groups were not restored by HUCB-MNCs. Increased PDE5 and reduced nNOS expressions in dutasteride groups were restored by HUCB-MNCs in the 12-week dutasteride group. eNOS and HIF-1α protein expression and serum total and free testosterone  levels were similar among groups. HUCB-MNCs reversed the decreased smooth muscle/collagen ratio in dutasteride-treated tissues. There was a significant increase in PDE5 and HIF-1α staining in 8-week dutasteride animals. CLINICAL TRANSLATION: This study demonstrates the corrective potential of HUCB-MNCs on some persistent structural and functional deterioration caused by 5ARI treatment in rats, which may encourage further evaluation of HUCB-MNCs in men with PPED. STRENGTHS AND LIMITATIONS: Therapeutic application of intracavernosal HUCB-MNCs is a novel approach for the rat model of post-5ARI ED. Lack of serum and tissue dihydrotestosterone measurements, vehicle injections and characterization of the cells remain limitations of our study. CONCLUSION: The persistent ED after prolonged administration of dutasteride in rats is reversed by HUCB-MNC treatment, which holds promise as a realistic therapeutic modality for this type of ED. Oztekin CV, Yilmaz-Oral D, Kaya-Sezginer E, et al. Beneficial Effects of Human Umbilical Cord Blood Mononuclear Cells on Persistent Erectile Dysfunction After Treatment of 5-Alpha Reductase Inhibitor in Rats. J Sex Med 2021;18:889-899.

Does the Intestinal Parasite Enterobius vermicularis Cause Acute Appendicitis?

OBJECTIVE: Although intestinal parasitic infections rarely cause acute appendicitis, they are common public health problems in undeveloped and developing countries. Parasitic infections should be kept in mind in patients clinically suspected of having acute appendicitis, and treatment procedures should be adopted according to the etiology. METHODS: Herein we presented the cases of four patients with clinical findings of acute appendicitis. Patients were clinically suspected of having acute appendicitis, and Enterobius vermicularis was detected in the pathological examinations of specimens. Pinworm infections are common parasitic infections that may mimic appendicitis. RESULTS: The pathology of the four cases was noted when the file of 186 patients aged between 4 and 72 years who underwent surgery for acute appendicitis in my hospital was retrospectively reviewed. When the appendectomy specimen was examined histopathologically it was understood that acute appendicitis was caused by Enterobius vermicularis parasite. CONCLUSION: In Enterobius infections, performing systemic therapy for patients and their family members is sufficient. To prevent unnecessary appendectomy, this type of infection should be made to ask in the history and clinical findings of patients.

Novel NLRP12 mutations associated with intestinal amyloidosis in a patient diagnosed with common variable immunodeficiency.

Heterozygous mutations in the NLRP12 gene have been found in patients with systemic auto-inflammatory diseases. However, the NLRP12-associated periodic fever syndromes show a wide clinical spectrum, including patients without classical diagnostic symptoms. Here, we report on a 20-year-old female patient diagnosed with common variable immunodeficiency (CVID), who developed intestinal amyloidosis and carried novel compound heterozygous mutations in NLRP12, identified by whole exome and transcriptome sequencing. CVID is a primary immunodeficiency characterized by low serum immunoglobulins, recurrent bacterial infections and development of malignancy, but it also presents with a magnitude of autoimmune features. Because of the unspecific heterogeneous clinical features of the disease, a delay in diagnosis is common. Secondary, inflammatory (AA type) amyloidosis has infrequently been observed in CVID patients. Based on our case observation and a critical review of the literature, we suggest that NLRP12 mutations might account for a small fraction of CVID patients with severe auto-inflammatory complications.