Praziquantel efficacy in mice infected with PZQ non‐susceptible S. mansoni isolate treated with artemether: parasitological,biochemical and immunohistochemical assessment

Botros SS, Hammam O, Mahmoud M, Bergquist R. Praziquantel efficacy in mice infected with PZQ non‐susceptible S. mansoni isolate treated with artemether: parasitological, biochemical and immunohistochemical assessment. APMIS 2010; 118: 692–702. Based on the fact that artemether (ART) affects immature schistosomes and that the effect of praziquantel (PZQ) mainly targets mature schistosomes, this work investigates the possible enhanced efficacy of PZQ in combination with ART in mice harboring a PZQ non‐susceptible Schistosoma mansoni isolate. Associated schistosomal, inflammatory, hepatic histopathological changes have been investigated by examining the tissue markers expressing apoptosis using FAS (CD95), anti‐apoptosis (Bcl2) and angiogenesis [vascular endothelial growth factor (VEGF)]. A batch of Swiss albino mice infected with a PZQ non‐susceptible (EE10) S. mansoni isolate was divided into 12 groups. Animals of the first group were left without treatment as infected controls, while groups 2–6 received PZQ in increasing doses. The animals of group 7 received ART in double doses. Those comprising groups 8–12 received combined therapy of PZQ and ART in the same doses and at the same timings postinfection (PI) as those belonging to groups 2–6. Parasitological parameters, liver function, and histopathological and immunohistochemical studies of FAS, Bcl2 and VEGF antibodies were assessed. Combined administration of ART and PZQ reduced the ED₅₀ (the dose at which the worm burden was decreased by 50%) of PZQ. Typical granulomas were not seen in animals treated with ART alone and combined with PZQ, with least expression of FAS and VEGF and increased expression of Bcl2. The minimal histopathological changes recorded in mice treated with both ART and PZQ could be related to a synergistic/additive effect of ART, markedly reducing the intensity of infection. Improved liver function tests support the less severe histopathological changes under the influence of this treatment protocol. This study encourages human trials especially in areas where malaria is not endemic, and differing combination doses should be investigated in view of the antagonistic effect noticed with some dose regimens.     

The rheological properties of different GNPs

Background  

Rheological analysis can be employed as a sensitive tool in predicting the physical properties of gold nanoparticles (GNPs). Understanding the rheological properties of GNPs can help to develop a better therapeutic cancer product, since these physical properties often link material formulation and processing stages with the ultimate end use. The rheological properties of GNPs have not been previously documented. The present study attempted to characterize the rheological properties of different sizes of GNPs at: 1) fixed temperature and wide range of shear rates; 2) varied temperature and fixed shear rate.     

CONJOINT CORPORA CAVERNOSA AND ITS ROLE IN ERECTION

The two penile corpora cavernosa (CC) remain as separate structures along the penile shaft. During our study of 28 cadavers, we came across three cadavers in which the two CCs were fused together forming a single tubular structure; this article discusses these three cadaveric specimens. The cadavers were aged 52, 36, and 12 years. After penile degloving, the dorsal groove on the penile shaft was absent. In two of the cadavers, multiple transverse cut-sections in the penile shaft showed that the two CCs were united into one single tubular structure that extended from the symphysis pubis to the glans penis. The cut section was kidney-shaped, with the corpus spongiosum lying under cover of the concave surface. No intercavernosal septum was identified. The transverse cut-section of the third cadaveric specimen revealed an incomplete fusion of the two CCs. An intercavernosal septum was present in its upper part, but absent in its lower part where the two CCs were fused together. In all three cadaveric specimens, the CCs showed a normal histologic pattern and the corpus spongiosum was morphologically normal. Based on biomechanical principles, we theorize that the blood volume occupying the two CCs would be greater, the penile rigidity stronger, and the penetration force more powerful in the two separate CCs as normal than in the two CCs if fused. However, further studies involving large number of cases are needed.     

Genetic variation in BCL-2 and response to interferon in hepatitis C virus type 4 patients

The prevalence of hepatitis C virus (HCV) infection varies across the world, with the highest number of infections reported in Egypt. BCL-2 gene polymorphism at codon 43 (127G/A) has been found to be a reliable and sensitive marker for the prediction of response to interferon therapy during viral infections. This study examined the correlation of BCL-2 gene polymorphism with the response to treatment with pegylated-IFN-alfa2b and ribavirin. Eighty patients with type 4 HCV and 40 healthy volunteers as controls were enrolled in a prospective study. Quantification of HCV-RNA by real-time PCR was performed for every patient, and gene polymorphism of BCL-2 (ala 43 Thr) was performed for all patients and controls. There was a statistically significant difference between non-responder patients and control group as regards the 43Thr genotype and allele (P<0.05). Also, there was a statistically significant difference between responders and non-responders (P<0.05) as regards 43Thr genotype and alleles. We conclude that BCL-2 gene polymorphism at codon 43 (127G/A) is a new biological marker to potentially identify responders and non-responders of HCV genotype 4 patients to achieving a sustained virological response to treatment with IFN in combination with ribavirin.     

Effect of leukotriene receptor antagonists on lung fibrosis in rats

To compare the effects of montelukast, prednisone and the combination of both drugs in a rat model of bleomycin-induced lung fibrosis. Rats, injected intravenously with bleomycin daily for five consecutive days, were treated with either montelukast, prednisone or a combination of both drugs orally daily for 35 days starting 14 days after the commencement of the first dose of bleomycin. Montelukast-treated rats showed reduction in collagen deposition by 29% and significant reduction in lung hydroxyproline content by 32%. Prednisone produced nonsignificant difference in collagen deposition and in lung hydroxyproline content compared with the bleomycin group. There was also a significant reduction in collagen deposition and hydroxyproline content in montelukast and prednisone treated rats by 15 and 17%, respectively, compared with bleomycin group. A significant reduction occurred in the mean area percentage of myofibroblast α smooth muscle actin in montelukast and montelukast and prednisone-treated groups by 41 and 37%, respectively, with nonsignificant difference in prednisone-treated rats as compared with the bleomycin group. Montelukast may be therapeutically effective for inhibiting further progression of lung fibrosis through inhibition of α-SMA positive myofibroblasts.     

Potential antifibrotic effects of AT1 receptor antagonist, losartan, and/or praziquantel on acute and chronic experimental liver fibrosis induced by Schistosoma mansoni

1. This study investigates the potential antifibrotic effect of losartan, AT-1 receptor antagonist, and/or praziquantel (PZQ) on acute and chronic hepatic fibrosis induced by Schistosoma mansoni (S. mansoni). 2. Schistosoma mansoni-infected mice were in two batches (I & II), each in four groups: (i) Infected untreated; (ii) treated with losartan, starting from the 4th or 12th weeks post-infection (PI); (iii) treated with PZQ in the 7th week PI; and (iv) treated with losartan, as group (ii) plus PZQ as group (iii). Comparable groups of uninfected mice were run in parallel with infected groups. Mice of batches I and II were killed 10 and 18 weeks PI, respectively. Hepatic content of hydroxyproline (HYP), serum levels and tissue expression of matrix metalloproteinase-2 (MMP-2), and transforming growth factor-β1 (TGF-β1) were determined. Parasitological, biochemical and histological parameters, which reflect disease severity and morbidity, were examined. 3. Losartan alone caused a considerable decrease in worm burden, hepatic tissue egg load with an increase in percentage of dead eggs, modulation of granuloma size and regression of inflammatory reactions, which was less obvious in the chronic stage. The best results were obtained when losartan was co-administered with PZQ, especially in the acute stage. This was revealed by a remarkable reduction in serum levels and tissue expression of MMP-2, TGF-β1 and HYP content, accompanied by conservation of hepatic reduced glutathione (GSH) versus the PZQ-treated group. 4. In conclusion, losartan has a promising antifibrotic action and could be introduced as a therapeutic tool with PZQ especially in acute schistosomal hepatic fibrosis.     

A Novel Concept for the Surgical Anatomy of the Perineal Body

Purpose Perineal body is considered by investigators as a fibromuscular structure that is the site of insertion of perineal muscles. We investigated the hypothesis that perineal body is the site across which perineal muscles pass uninterrupted from one side to the other. Methods Perineal body was studied in 56 cadaveric specimens (46 adults, 10 neonatal deaths) by direct dissection with the help of magnifying loupe, fine surgical instruments, and bright light. Results Perineal body consisted of three layers: 1) superficial layer, which consisted of fleshy fibers of the external anal sphincter extending across perineal body to become the bulbospongiosus muscle; 2) tendinous extension of superficial transverse perineal muscle crossing perineal body to contralateral superficial transverse perineal muscle, with which it formed a criss-cross pattern; and 3) tendinous fibers of the deep transverse perineal muscle; the fibers crossing perineal body decussated in criss-cross pattern with the contralateral deep transverse perineal muscle. A relation of levator ani or puborectalis muscles to perineal body could not be identified. Conclusions Perineal body (central perineal tendon) is not the site of insertion of perineal muscles but the site along which muscle fibers of these muscles and the external anal sphincter pass uninterrupted from one side to the other. Such a free passage from one muscle to the other seems to denote a “digastric pattern” for the perineal muscles. Perineal body is subjected to injury or continuous intra-abdominal pressure variations, which may eventually result in perineocele, enterocele, or sigmoidocele.     

Contraction of gluteal maximus muscle on increase of intra-abdominal pressure: role in the fecal continence mechanism

The gluteus maximus muscle (GMM) appears to contract with increased intra-abdominal pressure (IAP). The hypothesis that GMM contraction with increased IAP was investigated. The study comprised 32 healthy volunteers. IAP was measured by intravesical catheter. The response of electromyography of the GMM and external anal sphincter to sudden momentary and slow sustained straining was registered. The procedure was repeated after individual urinary bladder and GMM anesthetization. Sudden straining increased electromyographic activity of the external anal sphincter and GMM. Slow, sustained straining raised electromyographic activity of the gluteus maximus and external sphincter at differing degrees depending on straining intensity. The anesthetized gluteus maximus or urinary bladder did not respond to straining. The suggested GMM contraction on straining seems mediated through a reflex that is called "straining-gluteal reflex." This reflex appears to assist anal closure through extended and laterally rotated femur induced by gluteus contraction.     

Electromyographic activity of the anterolateral abdominal wall muscles during rectal filling and evacuation

BACKGROUND: The role of the anterolateral abdominal wall muscles (AAWMs) at defecation has not received sufficient attention in the literature. We investigated the hypothesis that the AAWMs exhibit increased electromyographic (EMG) activity on rectal distension, which presumably assists in rectal evacuation. MATERIALS AND METHODS: The effect of rectal balloon distension on the AAWMs EMG and on anal and rectal pressure was examined in 23 healthy volunteers (37.2 +/- 9.4 SD years, 14 men, 9 women); this effect was tested before and after rectal and AAWMs anesthetization. RESULTS: The rectal and anal pressures increased gradually upon incremental rectal balloon distension starting at 70 mL balloon distension until, at a mean of 113.6 +/- 5.6 mL, the balloon was expelled to the exterior. The AAWMs showed no EMG activity at rest or on rectal distension up to the time of balloon expulsion when they exhibited significant increase of EMG. This effect was abolished on individual rectal or AAWMs anesthetization but not with saline administration. CONCLUSIONS: AAWMs appear to contract simultaneously with rectal contraction; this action seems to increase the intra-abdominal pressure and assist rectal evacuation. The AAWMs contraction upon rectal contraction appears to be mediated through a reflex, which we call the "recto-abdominal wall reflex". Further studies are required to investigate the role of this reflex in defecation disorders.     

The effect of external urethral sphincter contraction on the cavernosus muscles and its role in the sexual act

Objectives/Aim A study of the effect of external urethral sphincter contraction on ischio-/bulbo-cavernosus muscles could not be traced in the literature. We investigated the hypothesis that external urethral sphincter contraction induces cavernosus muscles’ contraction. Methods Twenty-one healthy volunteers (age 37.6 ± 9.7 SD years, 12 men, nine women) were studied. The electromyographic response of the ischio- and bulbo-cavernosus muscles to external urethral sphincter stimulation was recorded before and after anesthetization of the external urethral sphincter, and the ischio- and bulbo-cavernosus muscles; the response was also recorded using normal saline instead of lidocaine. Results Upon external urethral sphincter stimulation (five square pulses, 1 ms duration, 53.8 ± 10.2 mA threshold), both cavernosus muscles exhibited increased electromyographic activity with a mean amplitude of 386.2 ± 44.9 μV for the ischio-cavernosus and 318.4 ± 36.6 μV for the bulbo-cavernosus muscle. The mean latency read 16.8 ± 1.3 ms for the ischio-cavernosus muscle and 15.7 ± 1.2 ms for the bulbo-cavernosus muscle. Neither the ischio- nor the bulbo-cavernosus muscle responded to stimulation of the anesthetized external urethral sphincter, but both responded after saline administration. Likewise, the anesthetized ischio- and bulbo-cavernosus muscles showed no response to external urethral sphincter stimulation but responded after saline had been injected. Conclusions Increased electromyographic activity of the two cavernosus muscles on external urethral sphincter stimulation presumably denotes contraction of these two muscles and that this action is probably reflex, mediated through the ‘sphinctero-cavernosus-reflex’. Cavernosus muscles’ contraction assists in the erectile and ejaculatory mechanisms. It is suggested that this reflex be included as an investigative tool in the diagnosis of erectile and ejaculatory disorders, provided further studies are performed.