Discovery of a potent and dual-selective bisubstrate inhibitor for protein arginine methyltransferase 4/5

Protein arginine methyltransferases (PRMTs) have been implicated in the progression of many diseases. Understanding substrate recognition and specificity of individual PRMT would facilitate the discovery of selective inhibitors towards future drug discovery. Herein, we reported the design and synthesis of bisubstrate analogues for PRMTs that incorporate a

Influence of age, body weight and season on testicular and epididymis biometrics in donkeys (Equus asinus) / Influencia de la edad, el peso corporal y la estación en la biometría testicular y el epidídimo en burros (Equus asinus)

SUMMARY: The objective of this present investigation was undertaken to study the testicular and epididymal biometrical characteristics in Algerian donkeys throughout the year according to age, body weight and seasonal changes. The study was conducted from February 2019 to January 2020. A total of 24 sexually mature donkeys (Equus asinus) were selected randomly. The testis and epididymis were collected after slaughter of donkeys and separated from the conjunctive and adherent tissues. The epididymis has been carefully removed at the testicular junction. In total, 10 biometric measures were selected and performed. Our results revealed that there are significant differences (P<0.05) between groups in most biometrics values. All biometric parameters varied throughout the year and were affected by the season. Significant differences of the GSI and SC values (P<0.05) were observed in different age groups and seasons. On the other hand, no significant differences were observed between the body weight categories of donkeys. The analysis of the correlation coefficients between the biometric values shows high positive correlations, ranged between 0.98 and 0.72 (P<0.001). There was a high positive correlation between age and all the parameters, ranged from 0.85 to 0.61 (P<0.001). However, there were low negative correlations between season and; testicular and epididymal biometrics. It is the first investigation that describes the male reproductive organs in donkeys of the Algerian race (Equus asinus), on the basis of biometric testicular and epididymal measurements. Our results showed that the essential differences were noted between some biometric parameters and the age, season and body weight of donkeys. In addition, the correlation coefficients were supported between biometric measurements and these factors. However, other approaches are necessary to undertake, such as histology of reproductive organs and hormone measurement, for a deeper understanding of the physiology of reproduction in donkeys.

RESUMEN: El objetivo de esta investigación fue estudiar las características biométricas testiculares y epididimarias en burros Argelinos durante todo el año de acuerdo con la edad, el peso corporal y los cambios estacionales. El estudio se realizó entre febrero de 2019 y enero de 2020. Se seleccionó al azar un total de 24 burros sexualmente maduros (Equus asinus). Los testículos y el epidídimo se recogieron después del sacrificio de los burros y se separaron de los tejidos conjuntivos y adherentes. El epidídimo se eliminó cuidadosamente en la unión testicular. En total, se seleccionaron y realizaron 10 medidas biométricas. Nuestros resultados revelaron que existen diferencias significativas (P <0,05) entre los grupos en la mayoría de los valores biométricos. Todos los parámetros biométricos variaron a lo largo del año y se vieron afectados por la temporada. Se observaron diferencias significativas de los valores de GSI y SC (P <0,05) en diferentes grupos de edad y estaciones. Por otra parte, no se observaron diferencias significativas entre las categorías de peso corporal de los burros. El análisis de los coeficientes de correlación entre los valores biométricos muestra altas correlaciones positivas, entre 0,98 y 0,72 (P <0,001). Hubo una alta correlación positiva entre la edad y todos los parámetros, que varió de 0,85 a 0,61 (P <0,001). Sin embargo, hubo bajas correlaciones negativas entre temporada y biometría testicular y epididimaria. Es la primera investigación que describe los órganos reproductores machos en burros de la raza Argelina (Equus asinus), sobre la base de mediciones biométricas testiculares y epididimarias. Nuestros resultados mostraron que se observaron las diferencias esenciales entre algunos parámetros biométricos y la edad, la estación y el peso corporal de los burros. Además, los coeficientes de correlación fueron compatibles entre las mediciones biométricas y estos factores. Sin embargo, son necesarios otros enfoques, como la histología de los órganos reproductivos y la medición de hormonas, para una mayor comprensión de la fisiología de la reproducción en burros.

Serum Resistin Levels in Nonalcoholic Fatty Liver Disease and their Relationship to Severity of Liver Disease

Background: Resistin is a hormone that is linked to the development of insulin resistance (IR); but information on the direct relationship of resistin levels in humans with nonalcoholic fatty liver disease (NAFLD); and their effect on the histological severity of NAFLD; is lacking. Objective: The aim of the current study is to determine the circulating resistin levels obtained from patients with NAFLD and to correlate them with insulin resistance and hepatic histological features. Methods: Blood samples were collected from 30 consecutive patients with liver-biopsy-proven NAFLD and 30 subjects as controls. Serum resistin levels were measured. Body mass index (BMI) was calculated for all subjects; and serum insulin; C-peptide; and lipoprotein levels were also measured. Results: Mean serum resistin level and BMI in the NAFLD group were significantly higher than in the controls (both P 0.001). Both men and women in the NAFLD group had higher mean serum resistin levels than did the men and women in the control group (all P 0.001). Multivariate analysis showed that the percentage of hepatic steatosis; sex; BMI; and homeostasis model assessment of insulin resistance [HOMA(IR)] were related to serum resistin levels. Conclusion: These data suggest increased resistin levels in NAFLD patients which are related to histological severity of the disease. These findings support the link between resistin; insulin resistance and BMI in these patients

Outcome of children older than one year with neuroblastoma

To assess the outcome of children older than one year with neuroblastoma treated at King Abdul-Aziz Medical City, Jeddah, Kingdom of Saudi Arabia. We retrospectively reviewed the files of 52 children older than one year with neuroblastoma [NBL] treated at our center between September 1987 and May 2003. Treatment consisted of OPEC chemotherapy regimen [vincristine, cisplatin, etoposide, and cyclophosphamide] or alternating OPEC/OJEC [carboplatin in place of cisplatin], surgical resection +/- radiotherapy [RT]. No patient received high dose therapy [HDT]. Thirty-four patients [65%] were stage 4, 12 [23%] stage 3, and 6 [11%] stage 2. Three stage 2 patients were treated with surgery only, all are alive in complete remission [CR]. All stage 3 and 4 patients were treated with chemotherapy and surgery +/- RT. After induction chemotherapy, CR was achieved in 17 patients [32%] and partial remission in 10 [19%]. Complete surgical resection was possible in 11 patients [22%]. Disease recurrence or progression occurred in 27 patients [51%]. With a median follow-up of 24 months [range 4-120], the 2-year event free survival was 10%, 82%, and 87% and the overall survival was 12%, 83%, and 100% for stage 4, 3, and 2. Children older than one year with localized NBL have good prognosis compared to those with stage 4. The use of HDT may improve the outcome in the latter group. Toxicity was significant, and adoption of risk-stratified treatment may help to reduce treatment complications

Simultaneous and non-simultaneous penetrating keratoplasty and cataract surgery for Fuchs' corneal endothelial dystrophy and cataract

To determine outcome of simultaneous and non-simultaneous penetrating keratoplasty and cataract surgery in eyes with Fuchs' dystrophy and cataract. The medical records of all patients with a histopathologically confirmed diagnosis of Fuchs' dystrophy who underwent penetrating keratoplasty at the University of Iowa Hospitals and Clinics between January 1, 1990 and December 31, 1999 and who had also undergone cataract extraction and intraocular lens implantation prior to December 31, 2001 were retrospectively reviewed. Patients were assigned to group 1 [cataract surgery followed by penetrating keratoplasty], group 2 [simultaneous penetrating keratoplasty and cataract surgery], and group 3 [penetrating keratoplasty followed by cataract surgery]. Two hundred and twelve eyes met the inclusion criteria. Among these, there were 48 cases in which cataract extraction and IOL implantation was performed prior to penetrating keratoplasty [group 1], 154 in which all three procedures were performed simultaneously [group 2], and 10 in which cataract surgery was performed after penetrating keratoplasty [group 3]. There were no statistically significant differences between the 3 groups with respect to the percentage of eyes that obtained a final visual acuity of 20/40 or better or 20/200 or worse. There were also no statistically significant differences between the 3 groups with respect to graft survival. Patients in group 3 were more likely to have refractive IOL predictability to within 2D of emmetropia than those in group 1 [80.0% vs. 56.1%] and those in group 2 [80.0% vs. 48.0%], but these differences were not statistically significant [P = 0.08, 0.09, respectively]. The performance of either simultaneous or non-simultaneous cataract surgery with penetrating keratoplasty in eyes with Fuchs' dystrophy has no significant effect on visual outcome or graft survival. Cataract surgery performed subsequent to penetrating keratoplasty is associated with a better refractive outcome

Stage 4S neuroblastoma, a disseminated tumor with excellent outcome

To review the clinical features and outcome of all cases of stage 4S neuroblastoma treated at our center. We retrospectively reviewed the files of all patients [n=75] with neuroblastoma treated at King Abdul-Aziz Medical City, Jeddah, Kingdom of Saudi Arabia between 1986 and 2005. We studied the clinical features and outcome of patients with stage 4S neuroblastoma. Six patients [8%] were confirmed to have stage 4S neuroblastoma. Three were boys with a median age at diagnosis of 4.5 months [range 28 days - 11 months]. Four patients required no intervention. The remaining 2 patients were treated with chemotherapy due to progressive hepatomegaly and respiratory distress. No patient required radiotherapy or surgical intervention. With a median follow up of 4 years [range 9 months - 15.5 years], all patients are alive and well. Two patients continue to have a residual abdominal mass, while complete resolution occurred in the others. Stage 4S neuroblastoma is a special tumor that carries excellent prognosis. Spontaneous regression may occur and intervention is only required in symptomatic patients

Role of reactive oxygen species in bradykinin-induced proliferation of vascular smooth muscle cells

In addition to the induction of cell proliferation and migration, bradykinin (BK) can increase c-fos mRNA expression, activate ERK 1/2 and generate reactive oxygen species (ROS) in vascular smooth muscle cells (VSMC). It is not known, however, whether BK can induce cellular proliferation and extracellular matrix production via redox-sensitive signaling pathways. We investigated the role(s) of ROS in proliferation, migration and collagen synthesis induced by BK in VSMC derived from Sprague Dawley rat aorta. BK (10 nM) increased VSMC proliferation by 30 % (n=5); this proliferation was inhibited by the antioxidants N-acetylcysteine (20 mM) and a-lipoic acid (LA, 250 mM). In addition, BK induced an increase in cell migration and in collagen levels that were blocked by LA. ROS production induced by BK (n=10) was significantly inhibited by bisindolylmaleimide (4mM) and by PD98059 (40mM). These results suggest that: 1) ROS participate in the mechanism(s) used by bradykinin to induce cellular proliferation; 2) bradykinin induces ROS generation through a pathway that involves the kinases PKC and MEK; and 3) ROS participate in the pathways mediating cell migration and the production of collagen as a response to treatment with bradykinin. To our knowledge, this is the first report describing mechanisms to explain the participation of ROS in the cellular proliferation and extracellular matrix pathway regulated by BK.

Ureteroscopy vs ESWL in the management of ureteric stones pro and conta!

In this retrospective study, we evaluated the results of rigid ureteroscopy and ESWL in the management of lower ureteric stones. One hundred and eighteen patients with ureteric stones were included in this study. Seventy eight patients were subjected to Ureteroscopic manipulations and forty patients to ESWL using Siemens Lithostar. The total success rate of ureteroscopy was 89.7%, compared to 62.5% with ESWL. There have been no significant late sequelae of the procedures. Transurethral ureteroscopy appears to offer an alternative to the existing therapeutic options, when in situ ESWL or push-pull technique through PCN is not successful

Intestinal complication of varicella infection

This paper discusses two cases of chickenpox with intestinal complications. The patient in the first case was exposed to necrosis and gangrene of part of the intestine with the result that a portion of the small intestine had to be removed. The patient in the second case suffered from acute appendicitis

Fracture of the penis and its surgical management

Rupture of the corpora cavernosa is an uncommon injury resulting from a direct blow to the fully erected penis. Only 200 cases have been reported in the world literature and this condition constitutes only one in every 175000 hospital admissions in the U.S.A. Although this condition is easily recognized, there is a great deal of controversy about its management. Conservative treatment is not satisfactory and is accompanied by a high incidence of late complications. In this study the work on 12 patients with this condition as regards predisposing and causative factors is reported. The way of management in the form of immediate surgical exploration, sharp trimming and primary repair of the tunica albuginea is also advocated with the use of a tunica vaginalis graft to patch defects in the tunica albuginea in the severe cases. The results are encouraging and the patients regained full erection after one month. The early surgical repair of the ruptured corpora cavernosa is recommended as the method of choice

Congenital nephrotic syndrome

Congenital Nephrotic Syndrome is a rare disorder in which inheritance is probably autosomal recessive, The most striking characteristic of congenital nephrotic syndrome, in contrast to that occuring later during childhood, is the resistance to corticosteroid therapy and the almost invariable fatal outcome. It appears to have a peculiarly high incidence in Scandinavian countries, particularly Finland. Often it is familial; maternal antibodies may be responsible as in Rh- incompatibility, it appear before the child first year; sometimes during the first few weeks of life. The course is progressive and few patients survive the first year of life. Death is usually due to renal failure or secondary infection. In this report, an Iraqi family with congenital nephrotic syndrome was thoroughly studied in one of them renal biopsy was done in UK. that confirmed the diagnosis