Embryonic differentiation of intestine in Indian goats (Capra hircus).

The present study focused on identifying knowledge gaps in scientific literature for developmental anatomy and future fetal-programming researches on goats. The aim of this study was to observe the sequential growth and the development of the intestine from stage of formation of preliminary digestive tube to the differentiation of various segments during early prenatal life in Indian goats. The developing digestive tube was first witnessed on the 23rd day of gestation histologically and from 25 days of gestation onwards, it became observable grossly under stereozoom microscope. The further stages of developing intestine rotation, herniation and coiling and re-entry stages were noticed on the 38th day, 41st day and 48th day of gestation, respectively. The first demarcation between small and large intestines in the form of cecal bulge was recorded at 41st day of gestation. On the 45th day of gestation, all the segments of intestine that is, duodenum, jejunum, ileum, caecum, colon and rectum were well demarcated. Microscopically, the wall of the digestive tube was composed of three layers; lamina epithelialis, pleuripotent blastemic tissue and the mesothelium in between 23 and 39 days of gestation. At 41st day of gestation, the blastemic tissue showed distinct separation into lamina propria-submucosa and tunica muscularis. Among connective tissue fibres only reticular fibres were observable in this study. The histochemical localisation of polysaccharides, bound lipids and alkaline phosphatase enzyme showed mild to moderate reaction. The reaction for acid phosphatase enzyme could not be observed or was absent in this study.

Use of the Woven EndoBridge Device for Sidewall Aneurysms: Systematic Review and Meta-analysis.

BACKGROUND: The Woven EndoBridge device was originally approved to treat intracranial wide-neck saccular bifurcation aneurysms. Recent studies have suggested its use for the treatment of sidewall intracranial aneurysms with variable success. PURPOSE: Our aim was to evaluate the safety and efficacy of the Woven EndoBridge device for sidewall aneurysms using a meta-analysis of the literature. DATA SOURCES: We performed a systematic review of all studies including patients treated with the Woven EndoBridge device for sidewall aneurysms from inception until May 2022 on Scopus, EMBASE, MEDLINE, the Web of Science, and the Cochrane Central Register of Controlled Trials. STUDY SELECTION: Ten studies were selected, and 285 patients with 288 sidewall aneurysms were included. DATA ANALYSIS: A random-effects meta-analysis of proportions using a generalized linear mixed model was performed as appropriate. Statistical heterogeneity across studies was assessed with I2 statistics. DATA SYNTHESIS: The adequate occlusion rate at last follow-up was 89% (95% CI, 81%-94%; I2, = 0%), the composite safety outcome was 8% (95% CI, 3%-17%; I2 = 34%), and the mortality rate was 2% (95% CI, 1%-7%; I2 = 0%). Aneurysm width (OR = 0.5; P = .03) was the only significant predictor of complete occlusion. LIMITATIONS: Given the level of evidence, our results should be interpreted cautiously until confirmation from larger prospective studies is obtained. CONCLUSIONS: The initial evidence evaluating the use of the Woven EndoBridge device for the treatment of wide-neck sidewall intracranial aneurysms has demonstrated high rates of adequate occlusion with low procedural complications. Our findings favor the consideration of the Woven EndoBridge device as an option for the treatment of sidewall aneurysms.

Assessment of occupational exposure to diesel particulate matter through evaluation of 1-nitropyrene and 1-aminopyrene in surface coal miners, India.

DPM (diesel particulate matter) is ubiquitously present in the mining environment and is known for mutagenicity and carcinogenicity to humans. However, its health effects in surface coal mines are not well studied, particularly in India. In this study, DPM exposure and corresponding exposure biomarkers were investigated in four different surface coal mines in Central India. To document and evaluate the DPM exposure in surface coal miners, we characterized 1-NP (1-nitropyrene) in the mining environment as surrogate for DPM using Sioutas Cascade Impactor. Exposure biomarkers were analyzed by collecting post work shift (8-h work shift) urine samples and determining the concentrations of 1-aminopyrene (1-AP) as a metabolite of 1-NP and 8-hydroxydeoxyguanosine (8OHdG) as DNA damage marker. We observed high concentration of 1-NP (7.13-52.46 ng/m3) in all the mines compared with the earlier reported values. The average creatinine corrected 1-AP and 8OHdG levels ranged 0.07-0.43 [Formula: see text]g/g and 32.47-64.16 [Formula: see text]g/g, respectively, in different mines. We found 1-AP in majority of the mine workers' urine (55.53%) and its level was higher than that reported for general environmental exposure in earlier studies. Thus, the study finding indicates occupational exposure to DPM in all the four mines. However, the association between 1-NP level and exposure biomarkers (1-AP and 8OHdG) was inconsistent, which may be due to individual physiological variations. The data on exposure levels in this study will help to understand the epidemiological risk assessment of DPM in surface coal miners. Further biomonitoring and cohort study are needed to exactly quantify the occupational health impacts caused by DPM among coal miners.

Targeting the paracrine hormone-dependent guanylate cyclase/cGMP/phosphodiesterases signaling pathway for colorectal cancer prevention.

Colorectal cancer (CRC) is one of the leading causes of cancer related-deaths. The risk of development of CRC is complex and multifactorial, and includes disruption of homeostasis of the intestinal epithelial layer mediated though dysregulations of tumor suppressing/promoting signaling pathways. Guanylate cyclase 2C (GUCY2C), a membrane-bound guanylate cyclase receptor, is present in the apical membranes of intestinal epithelial cells and maintains homeostasis. GUCY2C is activated upon binding of paracrine hormones (guanylin and uroguanylin) that lead to formation of cyclic GMP from GTP and activation of downstream signaling pathways that are associated with normal homeostasis. Dysregulation/suppression of the GUCY2C-mediated signaling promotes CRC tumorigenesis. High-calorie diet-induced obesity is associated with deficiency of guanylin expression and silencing of GUCY2C-signaling in colon epithelial cells, leading to tumorigenesis. Thus, GUCY2C agonists, such as linaclotide, exhibit considerable role in preventing CRC tumorigenesis. However, phosphodiesterases (PDEs) are elevated in intestinal epithelial cells during CRC tumorigenesis and block GUCY2C-mediated signaling by degrading cyclic GMP to 5`-GMP. PDE5-specific inhibitors, such as sildenafil, show considerable anti-tumorigenic potential against CRC by amplifying the GUCY2C/cGMP signaling pathway, but cannot achieve complete anti-tumorigenic effects. Hence, dual targeting the elevation of cGMP by providing paracrine hormone stimuli to GUCY2C and by inhibition of PDEs may be a better strategy for CRC prevention than alone. This review delineates the involvement of the GUCY2C/cGMP/PDEs signaling pathway in the homeostasis of intestinal epithelial cells. Further, the events are associated with dysregulation of this pathway during CRC tumorigenesis are also discussed. In addition, current updates on targeting the GUCY2C/cGMP/PDEs pathway with GUCY2C agonists and PDEs inhibitors for CRC prevention and treatment are described in detail.

Pre-symptomatic targeted treatment of patent ductus arteriosus in preterm newborns: A systematic review and meta-analysis.

BACKGROUND: A clinically significant patent ductus arteriosus (PDA) is associated with significant morbidity and mortality in premature newborns. Symptomatic PDAs are often treated with prostaglandin synthesis inhibitors (PSI), but controversy remains if PSIs should also be used to manage early, asymptomatic PDAs. OBJECTIVE: To systematically identify, critically appraise, and evaluate the efficacy and safety of pharmacological management of pre-symptomatic PDA in preterm newborns after confirmed patency by echocardiography. STUDY DESIGN: Systematic review and meta-analysis. SEARCH METHODS: We searched MEDLINE (Ovid), EMBASE (Ovid), Cochrane Central Register of Controlled Trials (Wiley), from date of inception to February 2017. Supplemental searching was performed in Scopus and Web of Science to identify additional relevant citations. We also searched conference proceedings, reference lists of relevant articles and the WHO International Clinical Trials Registry Platform (ICTRP). SELECTION CRITERIA: We included only randomized controlled trials (RCTs) that compared the use of indomethacin or ibuprofen to placebo for treatment of pre-symptomatic PDA in preterm newborns (<32 weeks gestational age and <1500gms). DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials, assessed risk of bias and extracted trial-level data. Outcomes are reported as risk ratios from random-effects models. Absolute risk reduction (ARR) is additionally reported for significant outcomes.We included seven trials (466 newborns). Targeted medical treatment did not significantly reduce mortality rates (RR 0.85, 95% CI 0.50 to 1.43; ARR -2.38%, 95% CI -8.04% to 3.29%; I2 0% 6 studies; 442 newborns), but it did significantly reduce the overall incidence of developing symptomatic PDA (RR 0.39, 95% CI 0.21 to 0.73; ARR -34.3%, 95% CI -50.8% to -17.8%; I2 0%; 3 studies; 97 newborns) compared to placebo. Other efficacy or safety outcomes were not significantly different. CONCLUSIONS: Targeted medical treatment of pre-symptomatic PDA decreases the incidence of developing symptomatic PDA, but not neonatal mortality. Further studies are essential to confirm these results.

Women's perspectives towards traditional and complementary medicine used to conceive, during pregnancy and the postpartum period.

OBJECTIVES: This study aims to explore pregnant and postpartum women's understanding of the meaning of traditional and complementary medicine (T&CM) and how that may affect their T&CM use. METHODS: A cross-sectional study was conducted using self-administered questionnaires. Data collected from 374 women were analysed and represented via descriptive statistics. RESULTS: Out of the 374 participants, 285 (76.2%) reported using at least one type of T&CM to conceive, during pregnancy or in the postpartum period. The majority of the participants identified that T&CM is all about plants or natural products without chemicals or drugs (n = 267, 71.4%, p < .001). The category of T&CM with the highest usage was biological based therapies (n = 272, 95.4%), while the lowest was energy therapies (n = 8, 2.8%). The most commonly used T&CM was the traditional Malay massage (n = 170, 59.6%). The main sources of information and recommendations for using T&CM came from their family members or friends (n = 199, 69.8%). Almost half of the participants incurred minimum expenditures of MYR100 and below on the T&CM used (n = 137, 48.1%) and there was no significant difference between pregnant and postpartum women (p = .056). CONCLUSION: This study reveals that many women are practising T&CM when trying to conceive and during pregnancy and the postpartum period even though they are aware that there is insufficient evidence on its safety and efficacy. Therefore, further studies are needed in order to gain sufficient clinical evidence that could be used to structure better guidelines for T&CM practices and services in Malaysia.

Ibrutinib downregulates a subset of miRNA leading to upregulation of tumor suppressors and inhibition of cell proliferation in chronic lymphocytic leukemia.

The lymph node (LN) is the site of chronic lymphocytic leukemia (CLL) cell activation and proliferation. Aberrant microRNA (miRNA) expression has been shown to have a role in CLL pathogenesis; however, a comparison of miRNA expression between CLL cells in the LN and the peripheral blood (PB) has previously not been reported. On the basis of the analysis of 17 paired LN and PB samples from CLL patients, we identify a panel of miRNAs that are increased in LN CLL cells correlating with an activation phenotype. When evaluated in CLL cells from 38 patients pre and post treatment with ibrutinib, a subset of these miRNAs (miR-22, miR-34a, miR-146b and miR-181b) was significantly decreased in response to ibrutinib. A concomitant increase in putative miRNA target transcripts (ARID1B, ARID2, ATM, CYLD, FOXP1, HDAC1, IBTK, PTEN and SMAD4) was also observed. Functional studies confirmed targets of ibrutinib-responsive miRNAs to include messenger RNA transcripts of multiple tumor suppressors. Knockdown of endogenous miR-34a and miR146b resulted in increased transcription of tumor suppressors and inhibition of cell proliferation. These findings demonstrate that ibrutinib downregulates the expression of a subset of miRNAs related to B-cell activation leading to increased expression of miRNA targets including tumor suppressors and a reduction in cell proliferation.

Study of Posterior Cerebral Artery in Human Cadaveric Brain.

Objective. Basilar artery (BA) terminates in right and left posterior cerebral arteries (PCAs). Each PCA supplies respective occipital lobe of the cerebrum. The present study is designed to know the morphology, morphometry, branching pattern, and symmetry of PCA. Methods. The study included 340 PCAs dissected from 170 human cadaveric brains. Results. Morphological variations of P1 segment included, aplasia (2.35%), hypoplasia (5.29%), duplication (2.35%), fenestration (1.17%), and common trunk shared with SCA (1.76%). Morphological variations of origin of P2 segment included direct origin of it from BA (1.17%) and ICA (2.35%). Unusually, two P2 segments, each arising separately from BA and ICA, were observed in 1.17%. Unilateral two P2 segments from CW were found in 0.58%. Morphological variations of course of P2 were duplication (0.58%), fenestration (0.58%), and aneurysm (1.76%). Unilateral P2 either adult or fetal was seen in 4.71%. The group II branching pattern was found to be most common. Asymmetry of P2 was 40%. Morphometry of P2 revealed mean length of 52 mm and mean diameter of 2.7 mm. Conclusion. The present study provides the complete anatomical description of PCA regarding morphology, morphometry, symmetry, and its branching pattern. Awareness of these variations is likely to be useful in cerebrovascular procedures.

Morphological study of chordae tendinae in human cadaveric hearts.

OBJECTIVES: The chordae tendinae (CT) are strong, fibrous connections between the valve leaflets and the papillary muscles. Dysfunction of the papillary muscles and chordae is frequent. Mitral valve replacement with preservation of CT and papillary muscles may preserve postoperative left ventricular function better than conventional mitral valve replacement in patients with chronic mitral regurgitation. METHODS: The study was carried out on 116 human cadaveric hearts. The heart was opened through the atrioventricular valve to view the constituents of the complex. Origin, attachments, insertions, distribution, branching pattern and gross structure of CT were observed and studied in detail. RESULTS: In the present study more than 21 terminologies of CT were defined by classifying it into six different types. Classification is done according to the origin, attachments, insertion, distribution, branching pattern and gross structure. Terminologies defined are as follows. Apical pillar chordae, Basal pillar chordae, True chordae, False chordae, Interpillar chordae, Pillar wall chordae, Cusp chordae, Cleft chordae, Commissural chordae, First order chordae, Second order chordae, Free zone chordae, Marginal chordae, Rough zone chordae, Straight chordae, Branched-fan shaped chordae, Spiral chordae, Irregular-web chordae, Tendinous chordae, Muscular chordae, Membranous chordae. Basal pillar chordae are found in 9.48%. Mean number of chordae taking origin from apical half of a single papillary muscle or single head of papillary muscle was 9.09 with the range of 3-18. Mean number of the marginal chordae attached to a single cusp was 22.63 ranging from 11 to 35. Strut chordae showed interesting insertion with broad aponeurosis in 38.79% and large muscular flaps in 13.79%. Chordae muscularis were found in 14% and membranous chordae were found in 6%. CONCLUSIONS: This knowledge may prove useful for cardiologists and cardiac surgeons.

Treatment-resistant recurrent membranoproliferative glomerulonephritis in renal allograft responding to rituximab: case report.

We report a case of idiopathic membranoproliferative glomerulonephritis (MPGN) recurring 2 years after a living-unrelated kidney transplantation. The disease was refractory to intravenous immunoglobulin and plasmapheresis. Treatment with 2 doses of rituximab resulted in remission of the disease. The disease relapsed 18 months later after an episode of cytomegalovirus pneumonitis. After treatment of the pneumonitis, a lung biopsy was performed owing to persistent chest symptoms, which revealed bronchiolitis obliterans with organizing pneumonia. Bone marrow examination and culture revealed presence of acid-fast bacilli, and culture grew Mycobacterium tuberculosis. A repeated course of rituximab was withheld because of infection with tuberculosis, the patient's chest symptoms, and rare reports of noninfectious lung disease after the use of rituximab. The patient continues to have proteinuria with impaired kidney function.

Postnatal developmental anatomy of testes and epididymis of Gaddi goats / Desarrollo anatómico postnatal de los testículos y epidídimo de cabras Gaddi

The study revealed that the testes of one-day-old Gaddi goats have descended in the scrotum along with adnexa. They were elongated compressed latero-medially and became ovoid during their postnatal growth and morphogenesis. The two testes were not different significantly in their weight and measurement. The average weight which was about 2.9 gm at birth grew to 107 gm (40X) in pubertal animals and nearly maintained it during the post-puberty (113 g). The mean length (1.46 cm), width (0.85 cm) and thickness (0.62 cm) also grew by 47, 60, and 83 times, respectively. In post-pubertal animals it measured 7.06 x 5.20 x 5.10 cm. The study indicated a very fast growth of the testes from birth to puberty, which did not alter significantly after that. A relatively much faster growth in thickness and width over the length was the reason behind the change of the morphology from more elongated shape at birth to ovoid shape on maturity. The mediastinum testis was grossly discernible in the testis even at birth. Epididymis was identifiable into caput, corpus and cauda. The gross linear mensuration of these components did not differ in the caput and cauda regions on either side, whereas the length of corpus was more on the left side in all age group of animals. The growth curve revealed a continuous growth of all segments, but the fastest growth occurred in the early postnatal life (at 12­18 month age).

El estudio reveló que los testículos de las cabras Gaddi, de un día de edad, descienden al escroto junto con sus anexos. Se elongaron en dirección latero-medial y convirtieron en ovoides durante su crecimiento postnatal y en la morfogénesis. Los dos testículos no fueron significativamente diferentes en su peso y medidas. El peso promedio fue aproximadamente de 2,9 g al nacer, y aumentó a 107 g (40X) en animales púberes y casi mantuvo su peso durante la post-pubertad (113 g). La longitud (1,46 cm), ancho (0,85 cm) y espesor (0,62 cm) también crecieron unas 47, 60 y 83 veces, respectivamente. En los animales post-puberales las medidas fueron de 7,06 x 5,20 x 5.10 cm. Se observó un crecimiento muy rápido de los testículos desde el nacimiento hasta la pubertad, sin alterarse de manera significativa posteriormente. Un crecimiento relativamente mucho más rápido en espesor y anchura, sobre la longitud, fue la razón detrás del cambio de la morfología desde la forma más alargada, presente en el nacimiento, a la forma ovoide de la madurez. El mediastino testicular fue claramente identificado en el testículo, inclusive en el nacimiento. En el epidídimo se identificaron las porciones de la cabeza, cuerpo y cola. La medición lineal de estos componentes no difirió en las regiones de la cabeza y cola de cada lado, mientras que la longitud del cuerpo fue mayor en el lado izquierdo en todos los grupos. La curva de crecimiento reveló un crecimiento continuo de todos los segmentos, pero el mayor crecimiento se produjo en la vida postnatal temprana (entre los 12 y 18 meses).

Anatomical variations of the circulus arteriosus in cadaveric human brains.

Objective. Circulus arteriosus/circle of Willis (CW) is a polygonal anastomotic channel at the base of the brain which unites the internal carotid and vertebrobasilar system. It maintains the steady and constant supply to the brain. The variations of CW are seen often. The Aim of the present work is to find out the percentage of normal pattern of CW, and the frequency of variations of the CW and to study the morphological and morphometric aspects of all components of CW. Methods. Circulus arteriosus of 150 formalin preserved brains were dissected. Dimensions of all the components forming circles were measured. Variations of all the segments were noted and well photographed. The variations such as aplasia, hypoplasia, duplication, fenestrations, and difference in dimensions with opposite segments were noted. The data collected in the study was analyzed. Results. Twenty-one different types of CW were found in the present study. Normal and complete CW was found in 60%. CW with gross morphological variations was seen in 40%. Maximum variations were seen in the PCoA followed by the ACoA in 50% and 40%, respectively. Conclusion. As it confirms high percentage of variations, all surgical interventions should be preceded by angiography. Awareness of these anatomical variations is important in neurovascular procedures.

Ibrutinib-induced lymphocytosis in patients with chronic lymphocytic leukemia: correlative analyses from a phase II study.

Ibrutinib and other targeted inhibitors of B-cell receptor signaling achieve impressive clinical results for patients with chronic lymphocytic leukemia (CLL). A treatment-induced rise in absolute lymphocyte count (ALC) has emerged as a class effect of kinase inhibitors in CLL and warrants further investigation. Here we report correlative studies in 64 patients with CLL treated with ibrutinib. We quantified tumor burden in blood, lymph nodes (LNs), spleen and bone marrow, assessed phenotypic changes of circulating cells and measured whole-blood viscosity. With just one dose of ibrutinib, the average increase in ALC was 66%, and in>40% of patients the ALC peaked within 24 h of initiating treatment. Circulating CLL cells on day 2 showed increased Ki67 and CD38 expression, indicating an efflux of tumor cells from the tissue compartments into the blood. The kinetics and degree of the treatment-induced lymphocytosis was highly variable; interestingly, in patients with a high baseline ALC the relative increase was mild and resolution rapid. After two cycles of treatment the disease burden in the LN, bone marrow and spleen decreased irrespective of the relative change in ALC. Whole-blood viscosity was dependent on both ALC and hemoglobin. No adverse events were attributed to the lymphocytosis.

Gross anatomical studies on the adrenal gland in prenatal goat (Capra Hircus) / Estudio anatómico macroscópico de la glándula suprarrenal en fetos de cabra (Capra Hircus)

The present study was conducted on the 24 healthy and normal embryos/foeti of non- descript goat (Capra hircus) varying from day old to 150 days of gestation. The embryo/foeti were assigned into three groups according to their gestational ages; Groups I (0-50 days), II (51-100 days) and III (101-till term). At 38 days of gestation the primordia of right and left adrenal gland were observed as a pea shaped spherical swelling located just cranial to the respective metanephros. Biometrical studies revealed the increase in the all parameters of the adrenal gland with the advancement of age. Adrenal glands were harvested first grossly at 50 days of gestation.

El presente estudio se realizó en 24 embriones / fetos de cabra (Capra hircus) sanos de un día hasta los 150 días de gestación. Los embriónes fueron separados en tres grupos de acuerdo a la edad gestacional: grupos I (0-50 días), II (51 a 100 días) y III (101-till plazo). A los 38 días de gestación se observó el primordio de las glándulas suprarrenales derecha e izquierda como una protuberancia de forma esférica, situada justo en la zona craneal en relación al metanefros. C on el avance de la edad, estudios biométricos revelan aumento de todos los parámetros de la glándula suprarrenal. Las glándulas suprarrenales fueron extraídas inicialmente a los 50 días de gestación.

Postnatal development of testis in gaddi goat (capra hircus) / Desarrollo postnatal del testículo en la cabra gaddi (capra hircus)

A study was conducted on the testicles of 30 male Gaddi goats, divided into 3 groups viz; prepubertal (0 day to 18 months), pubertal (<18 months to >5 yrs) and post- pubertal (>5 yrs) ages. The study revealed that the testis was covered by fibroserous tunica albuginia having outer fibrous layer and inner vascular layer with smooth muscle fibers at birth. The tunica albuginia continuously grew in thickness from prepubertal to postpubertal animals. The septula testis arising from the tunica albuginia, divided the parenchyma in lobules and converged at mediastinum testis. Few differentiated and undifferentiated Leydig cells were present in the intertubular spaces of neonates, which enormously increased in pubertal animals and replaced by fibroblasts in the postpubertal animals. The parenchyma comprised of solid sex cords in new born kids. These were converted into luminated tubules after 6 months of age and had clear cut tubuli contorti and tubuli recti leading to the mediastinum testis. In "0" day old kids, sex cords were filled with undifferentiated small cells located peripherally along the basement membrane and large primordial germ cells located centrally. By six months of age, latter started showing sign of degeneration and thus luminization of tubules started. Spermatogenesis startedin the seminiferous tubules of 12-18 months goat. In pubertal animals all the stages of spermatogenic cells and Sertoli cells were identified in the seminiferous tubules. The population of gonia cells and primary + secondary spermatocytes were 35% and 30% respectively. In postpubertal animals gonia cells were reduced to <30% and Primary + secondary spermatocytes were <20%. Many degenerating seminiferous tubules showed hyalinization, fibrosis and giant cells. The stroma and parenchyma ratio which was 35:65 at birth became 30:60 at 6 months, 25:75 at 12 months and 15:85 in pubertal and 20:80 in postpubertal animals. Increased stroma in last phase was associated with replacement of seminiuferous tubules by fibrous elements.

Se realizó un estudio en 30 testículos de cabras Gaddi machos divididos en 3 grupos: prepúberes (0 días a 18 meses), púberes (<18 meses y >5 años) y post-púberes (>5 años). El estudio reveló que los testículos al nacimiento estaban cubiertos por una túnica albugínea fibroserosa con una capa fibrosa externa y otra capa vascular interna con fibras musculares lisas. En los animales prepúberes hasta los pospúberes, la túnica albugínea mostró un crecimiento continuo de espesor. El septo testicular derivado de la túnica albugínea, divide el parénquima en lóbulos convergentes en el mediastino testicular. En los espacios intertubulares de los testículos de los recién nacidos, se observaron escasas células interticiales diferenciadas e indiferenciadas, sin embargo, se registró un aumento importante en los animales púberes las cuales fueron reemplazadas por fibroblastos después de la pubertad. El parénquima en los testículos de los animales recién nacidos estaba compuesto por cordones sexuales continuos. Estos se convierten en túbulos luminados después de los 6 meses de edad, evidenciando túbulos contorneados y rectos que conducen al mediastino testicular. En animales de 0 días de edad, los cordones sexuales presentaban pequeñas células no diferenciadas y situadas periféricamente a lo largo de la membrana basal y grandes células germinales primordiales céntricas. A los seis meses de edad, este último comenzó a mostrar signos de degeneración. La espermatogénesis se inició en los túbulos seminíferos desde los 12 a 18 meses de edad. En los animales púberes se identificaron en los túbulos seminíferos todas las etapas de las células de espermatogénesis y células sustentaculares. La población de células gonia fue del 35% y de espermatocitos primarios más secundarios 30%. En los animales pospúberes las células gonia se redujeron a <30% y espermatocitos primarios más secundarios a < 20%. Muchos túbulos seminíferos presentaron degeneración. La relación parénquima/estroma fue 35:65 al nacer, luego de 30:60 a los 6 meses, de 25:75 a los 12 meses, de 15:85 en animales prepúberes y 20:80 en la pubertad. El aumento del estroma en la última fase fue asociado con el reemplazo de los túbulos seminíferos por elementos fibrosos.

Morphine stimulates platelet-derived growth factor receptor-ß signalling in mesangial cells in vitro and transgenic sickle mouse kidney in vivo.

BACKGROUND: Pain and renal dysfunction occur in sickle cell disease. Morphine used to treat pain also co-activates platelet-derived growth factor receptor-ß (PDGFR-ß), which can adversely affect renal disease. We examined the influence of morphine in mesangial cells in vitro and in mouse kidneys in vivo. METHODS: > Mouse mesangial cells treated with 1 µM morphine in vitro or kidneys of transgenic homozygous or hemizygous sickle or control mice (n=3 for each), treated with morphine (0.75, 1.4, 2.14, 2.8, 3.6, and 4.3 mg kg(-1) day(-1) in two divided doses during the first, second, third, fourth, fifth, and sixth weeks, respectively), were used. Western blotting, bromylated deoxy uridine incorporation-based cell proliferation assay, reverse transcriptase-polymerase chain reaction, immunofluorescent microscopy, and blood/urine chemistry were used to analyse signalling, cell proliferation, opioid receptor (OP) expression, and renal function. RESULTS: Morphine stimulated phosphorylation of PDGFR-ß and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) to the same extent as induced by platelet-derived growth factor-BB (PDGF-BB) and promoted a two-fold increase in mesangial cell proliferation. The PDGFR-ß inhibitor, AG1296, OP antagonists, and silencing of µ- and κ-OP abrogated morphine-induced MAPK/ERK phosphorylation and proliferation by ~100%. Morphine treatment of transgenic mice resulted in phosphorylation of PDGFR-ß, MAPK/ERK, and signal transducer and activator of transcription 3 (Stat3) in the kidneys. Morphine inhibited micturition and blood urea nitrogen (BUN) clearance and increased BUN and urinary protein in sickle mice. CONCLUSION: Morphine stimulates mitogenic signalling leading to mesangial cell proliferation and promotes renal dysfunction in sickle mice.

Prenatal development of pelvic urethra in goat (Capra hircus) / Desarrollo prenatal de la uretra pélvica en cabras (Capra hircus)

The study was conducted on the embryo/foeti of goat from 0-150 days of gestation, divided into group I (0-30 days), group II (31-60 days), group III (61-90 days), group IV (91-120 days) and group V (121-150 days of gestation). In group I whole embryo was processed and serial sections were cut whereas, in rest of the groups, pelvic urethra was dissected out and the tissues from the representative areas were used for the study. Grossly, on 49.33 days of gestation the pelvic urethra was present in the form of smooth cylindrical tube, approximately 4mm in length. The primordial of vesicular gland and bulbourethral gland appeared on 52 days of gestation at the junction of neck of urinary bladder with pelvic urethra and at the junction of pelvic and penile urethra respectively. The length, width, height and circumference of pelvic urethra increased with increased in gestation period, however the length (7 times) and circumference (9 times) increased maximum from group II to group V. The morphometrical parameters (length, width, height and circumference) of pelvic urethra were significantly correlated with the age and weight of foetus throughout gestation period. The colliculus seminalis, which was present in the form of ridge on 72 days of gestation, became distinct on 75 days of gestation. Histologically, on 28 days of gestation, the urogenital sinus was present as a cleft with in the cluster of cells. On 55 days of gestation, the process of luminization started with in the wall of pelvic urethra, which started first in its caudal part and proceeded cranially. All the four layers (Tunica mucosa, submucosa, muscularis and adventitia) were distinct. The lumen was lined with 3-4 layers of stratified epitheliumin group II but in group III on 70 days of gestation and beyond this distinct transitional epithelium was present. The formation of cavernous spaces started at 59 days of gestation...

El estudio se realizó sobre embriones/fetos de cabras de 0 a 150 días de gestación, divididos en grupo I (0-30 días), grupo II (31-60 días), el grupo III (61-90 días), grupo IV (91 a 120 días) y grupo V (121-150 días de gestación). En el grupo I embriones enteros fueron procesados mediante cortes seriados, en el resto de los grupos, la uretra pélvica fue disecada y los tejidos de las áreas representativas se utilizaron para su estudio. Macroscópicamente, a los 49,33 días de gestación de la uretra pélvica estaba presente en forma de tubo cilíndrico liso, aproximadamente 4 mm de longitud. El primordio de la glándula vesicular y la glándula bulbouretral apareció a los 52 días de gestación en el cruce de cuello de la vejiga urinaria con la uretra pélvica y el cruce de la uretra pélvica y pene respectivamente. La longitud, ancho, alto y circunferencia de la uretra pélvica aumentó con el avance del período de gestación, sin embargo, la longitud (7 veces) y el perímetro (9 veces) aumentó en el grupo II y V. Los parámetros morfométricos (longitud, ancho, alto y circunferencia) de la uretra pélvica se correlacionaron significativamente con la edad y el peso del feto durante toda la gestación. El colículo seminal, que estaba presente en la forma de cresta a los 72 días de gestación, se mostró distinta a los 75 días de gestación. Histológicamente, en 28 días de gestación, el seno urogenital estaba presente como una hendidura con un grupo de células. En 55 días de gestación, el proceso de luminización comenzó en la pared de la uretra pélvica, que comenzó en su primera parte caudal y procedió cranealmente. Las cuatro capas (túnica mucosa, submucosa, muscular y adventicia) eran distintas. La luz estaba cubierta con 3-4 capas de epitelio estratificado en el grupo II, pero en el grupo III a los 70 días de gestación y más, un epitelio de transición distinto estuvo presente. La formación de espacios cavernosos comenzó a los 59 días de gestación...