Does vitamin D supplementation benefit patients with type 1 diabetes mellitus who are vitamin D deficient? A study was performed at the Sudan Childhood Diabetes Center from 2019 to 2022.

Objectives: Type 1 diabetes mellitus is a chronic autoimmune disease caused by insufficient production of insulin. Many studies have linked type 1 diabetes mellitus to vitamin D3 deficiency. We investigated the prevalence of vitamin D deficiency in Sudanese children and adolescents with type 1 diabetes mellitus and assessed the impact of vitamin D deficiency treatment on their glycemic control. Methods: In 2019-2022, we conducted a quasi-experimental study on 115 children with type 1 diabetes mellitus (1-19 years old) at the Sudan Childhood Diabetes Center. Vitamin D supplements were given orally to deficient patients for 3 months. The concentrations of hemoglobin A1c, fasting blood glucose, insulin dosage, and vitamin D (25-hydroxyvitamin D (25(OH)D)) were measured before and after vitamin D3 administration. One-way ANOVA and paired sample t-tests were used to evaluate the effect of supplementation. Results: Only 27% of type 1 diabetes mellitus children were deficient in vitamin D, whereas 31.1% were inadequate and 40.9% were sufficient. The administration of vitamin D supplements slightly improved hemoglobin A1c levels in 67.7% of the patients, but the difference was not significant (mean 10.8 ± 2.1% before, 10.1 ± 2.5% after, p0.05 = 0.199). However, there was a significant decrease in the fasting blood glucose level (mean: 174.978.5-136.759.1 ng/ml; p0.05 = 0.049). Vitamin D levels were significantly increased after treatment (mean = 49.6 ng/mL; t-test = -11.6, 95% CI 40.8-(-28.6); p0.05 = 0.000). After vitamin D3 supplementation, 25.8% of individuals changed their insulin dosage; however, there was no significant variation in insulin needs. Conclusions: The prevalence of vitamin D deficiency in children and adolescents with type 1 diabetes mellitus in Sudan is relatively high; incorporating vitamin D supplements in their treatment plan may improve their glycemic control.

An Incidental Diagnosis of Extraosseous Ewing's Sarcoma in the Kidney.

Ewing's sarcoma is generally observed in the skeletal and connective tissues of paediatric individuals. The occurrence of extraosseous neuroectodermal tumours is uncommon. Renal Ewing's sarcoma usually presents with flank pain, haematuria, or as an abdominal mass. Immunohistochemistry and fluorescence in situ hybridization (FISH) techniques are essential in its diagnosis and differentiation from other tumours. We present asymptomatic renal Ewing's sarcoma in a 19-year-old female patient who was diagnosed incidentally, and the CT scan confirmed a 2.8 cm left mid-pole renal mass suggestive of malignancy. She was managed with a robotic partial nephrectomy. Tumour immunohistochemistry and the FISH technique confirmed the diagnosis of Ewing's sarcoma. The patient made an uneventful recovery and was referred for chemotherapy. This case report illustrates that despite the aggressiveness of the tumour, it can be detected earlier despite an asymptomatic presentation and be successfully treated with nephron-sparing surgery and chemotherapy.

The Management of Bacillus Calmette-Guérin (BCG) Failure in High-Risk Non-muscle Invasive Bladder Cancer: A Review Article.

Non-muscle invasive bladder cancer (NMIBC) is a common urological malignancy, and bacillus Calmette-Guérin (BCG) therapy is the gold standard treatment in intermediate and high-risk groups. However, BCG failure occurs in a significant proportion of patients, emphasizing the need for effective alternative treatment modalities to address this burden. These treatments include immunotherapy, enhanced drug delivery, targeted therapy, device-assisted chemotherapy, vaccine therapy, and gene therapy, which show varying degrees of safety and efficacy. The objective of this review is to summarize the current evidence and ongoing research on these emerging therapies, offering insight into their potential for improving patient outcomes and quality of life. Although radical cystectomy remains the standard of care for high-risk NMIBC patients unresponsive to BCG, novel treatment modalities hold promise for the future management of this challenging patient population.

Outcome of topiramate in migraine prophylaxis.

Topiramate is an antiepileptic medication originally and one of the first-line drugs for migraine prophylaxis. Herein, we aimed to assess the outcome of topiramate in migraine prophylaxis by evaluating the reduction in frequency and/or severity of attacks and addressing the most common adverse effects associated with it. Methods: A descriptive, prospective hospital-based study was conducted at Ibrahim Malik Hospital, National Center of Neurological Disease and Sciences from October 2018 to May 2019. A comprehensive, structural, close-ended questionnaire was used to collect data on demographics, clinical, risk factors, treatment, side effects, and outcome. Results: This study covered 32 study participants; the mean age was 33±10 years, with a female predominance of 27 (84%). Nearly, half of them 15 (47%) migraine triggered by weather changes, and 13 (41%) had menstruation. About 17 (53%) was suffering from headache more than 24 months and most of them 26 (81%) used over-the-counter medications for acute pain headache. The mean frequency of attacks per month was reduced from 6.1 baselines to 3.2, in the severity means was 6.9 turns to 5. Reduction in frequency of attacks there was significant in both number and severity (P<0.001) with no significant difference in 50 and 100 mg doses. Concerning adverse effects, 5 (15.6%) did not complain of any, more than a third 12 (38%) experienced weight loss, 7 (22%) both abdominal/gastrointestinal symptoms and dizziness, 5 (16%) mood changes, 4 (13%) both paresthesia and decreased memory, 3 (9%) both anorexia and sleepiness. Conclusion: Topiramate is effective in reducing headache frequency and reasonably well tolerated in adult Sudanese patients with episodic migraine. This may provide good evidence to support its use in routine clinical management.

PMUTs Arrays for Structural Health Monitoring of Bolted-Joints.

Micro-electro-mechanical systems (MEMS) have enabled new techniques for the miniaturization of sensors suitable for Structural Health Monitoring (SHM) applications. In this study, MEMS-based sensors, specifically Piezoelectric Micromachined Ultrasonic Transducers (PMUT), are used to evaluate and monitor the pre-tensioning of a bolted joint structural system. For bolted joints to function properly, it is essential to maintain a suitable level of pre-tensioning. In this work, an array of PMUTs attached to the head and to the end of a bolt, serve as transmitter and receiver, respectively, in a pitch-catch Ultrasonic Testing (UT) scenario. The primary objective is to detect the Change in Time of Flight (CTOF) of the acoustic wave generated by the PMUT array and propagating along the bolt's axis between a non-loaded bolt and a bolt in service. To model the pre-tensioning of bolted joints and the transmission of the acoustic wave to and from a group of PMUTs through the bolt, a set of numerical models is created. The CTOF is found to be linearly related to the amount of pre-tensioning. The numerical model is validated through comparisons with the results of a preliminary experimental campaign.

Clinical profile and risk factors of cerebral venous sinus thrombosis (CVST) in Sudan: A multicenter cross-sectional study.

Background: Cerebral venous sinus thrombosis (CVST) is a relatively uncommon cause of stroke that mainly affects young ladies, with a wide spectrum of symptoms severity, and prognosis. In this study, we aim to study the clinical profile and Risk Factors of CVST among Sudanese patients in Khartoum state hospitals. Methods: This was a multi-center cross-sectional hospital-based study that covered 37 participants in three major hospitals in Khartoum, with radiologically confirmed Cerebral Venous Sinus Thrombosis (CVST). Results: About 37 patients were included in this study. The median age was 35 years; the range was 52 years, with a minimum age of 23 years and a maximum of 75 years. The commonest presenting feature was headache (n = 35; 94.6%), followed by blurring of vision (n = 25; 67.6%), while seizures is a presenting symptom in nearly half of the patients (n = 17; 45.9%), on examination papilledema was present in 83.8%. In this study 13.8% were pregnant, 31.0% were postpartum and OCPS users account for 27%. Regarding the involved sinus; Sagittal Venous Sinus and the transverse sinus were the most affected sinuses. Regarding treatment options: "low molecular weight heparin followed with warfarin" was found in 81.1%, followed by heparin in only 10.8%, while the new agents NOACs comprised only 8.1%. Conclusion: Cerebral Venous Sinus Thrombosis is mainly a disease of child-bearing women, although significant proportions of men were affected. Cerebral Venous Sinus Thrombosis presents in a wide variety of signs and symptoms.

Efficient Modeling and Simulation of PMUT Arrays in Various Ambients.

This paper presents a numerical reduced-order modeling (ROM) approach for complex multi-layered arrays of piezoelectric micromachined ultrasonic transducers (PMUTs). The numerical modeling technique adopted to generate an array of PMUTs consisting of a considerable number of transducers allows for a large reduction in computational cost without reducing accuracy. The modeling idea is based on coupling shell elements applied to the PMUT structural layers with 3D-solid elements applied to the piezoelectric layer. A set of eigenfrequency and frequency domain analyses are presented considering a single ROM of a PMUT performing in different ambients and the performing central frequencies are obtained for every considered scenario. A unique arrangement of 228 PMUTs is presented and tested for its ability to transmit and receive acoustic waves. The operating frequency band of the array and the level of interference and cross-talk among different PMUTs in the near field are estimated. Finally, the results from a preliminary experimental test performed to analyze the acoustic abilities of an 8 × 8 array of PMUTs are presented. A corresponding numerical model is created and the obtained results matched the experimental data, leading to a validation of the modeling technique proposed in this work.

Neurological manifestations of COVID-19: A potential gate to the determinants of a poor prognosis.

BACKGROUND: Several investigations were carried out during the pandemic, demonstrating a number of neurological symptoms linked to coronavirus disease 2019 (COVID-19) infection. OBJECTIVES: The goal of this review is to discuss COVID-19 disease's neurological signs and squeals. METHODOLOGY: From December 2019 to May 2020, data were retrieved from PubMed, Scopus, and ScienceDirect, as well as a manual search using Google Scholar. COVID-19, neurological symptoms, cranial nerves, motor system were among the key phrases utilized in the search. RESULTS: The intensity of respiratory involvement increases the likelihood of neurological symptoms and consequences. According to some research, it might range from 34% to 80%. The central and peripheral neural systems are both affected, resulting in cranial nerve palsies and limb paralysis. CONCLUSION: COVID-19 neurologic complications are key drivers of patient severity and mortality. Headache, convulsions, mental and psychic disorders, delirium, and insomnia are just some of the symptoms that the virus can cause. The olfactory nerve is the most commonly damaged cranial nerve, resulting in anosmia. Stroke (mostly infarction), encephalitis, meningitis, Guillain-Barre syndrome, relapse of multiple sclerosis, and transverse myelitis are all symptoms and squeals.

Detection of Radiation-Induced DNA Damage in Breast Cancer Patients by Using Gamma H2AX Biomarker: A Possible Correlation with Their Body Mass Index.

Radiotherapy is one of the most important options for treating breast cancer in humans. The development of biomarkers to monitor radiosensitivity is scarce. The aim of this study is to investigate the γH2AX levels in the human blood samples 0.5 h after radiotherapy compared to the levels before radiotherapy in breast cancer patients in relation to their respective body mass index (BMI). Blood plasma samples were collected from a total of 20 breast cancer patients before and after radiotherapy to measure γH2AX levels with an antibody against γH2AX based on enzyme-linked immunosorbent assay technique. The median BMI of the patients was 30 kg/m2. γH2AX was differentially expressed in breast cancer patients before radiotherapy. γH2AX levels significantly increased in 14 patients after radiotherapy (P = 0.006), whereas γH2AX levels decreased in three patients after radiotherapy, and three patients were excluded. There was no correlation between γH2AX values after radiotherapy and BMI (P = 0.5, r = 0.1). Our results suggest that γH2AX can be used by ELISA technique to measure γH2AX in the blood plasma of breast cancer patients undergoing radiotherapy and can be considered a biomarker of radiosensitivity.

Involvement of ADGRV1 Gene in Familial Forms of Genetic Generalized Epilepsy.

Background: Genetic generalized epilepsies (GGE) including childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), and GGE with tonic-clonic seizures alone (GGE-TCS), are common types of epilepsy mostly determined by a polygenic mode of inheritance. Recent studies showed that susceptibility genes for GGE are numerous, and their variants rare, challenging their identification. In this study, we aimed to assess GGE genetic etiology in a Sudanese population. Methods: We performed whole-exome sequencing (WES) on DNA of 40 patients from 20 Sudanese families with GGE searching for candidate susceptibility variants, which were prioritized by CADD software and functional features of the corresponding gene. We assessed their segregation in 138 individuals and performed genotype-phenotype correlations. Results: In a family including three sibs with GGE-TCS, we identified a rare missense variant in ADGRV1 encoding an adhesion G protein-coupled receptor V1, which was already involved in the autosomal recessive Usher type C syndrome. In addition, five other ADGRV1 rare missense variants were identified in four additional families and absent from 119 Sudanese controls. In one of these families, an ADGRV1 variant was found at a homozygous state, in a female more severely affected than her heterozygous brother, suggesting a gene dosage effect. In the five families, GGE phenotype was statistically associated with ADGRV1 variants (0R = 0.9 103). Conclusion: This study highly supports, for the first time, the involvement of ADGRV1 missense variants in familial GGE and that ADGRV1 is a susceptibility gene for CAE/JAE and GGE-TCS phenotypes.

Surgical and radiological predictive factors for ureteric stricture formation in patients treated with ureteroscopy for ureteric stones.

BACKGROUND: Ureteric stricture is a potential complication of impacted ureteric stones. This study investigates surgical and radiological factors that could predict ureteric stricture formation after ureteroscopic treatment of impacted ureteric stones. MATERIALS AND METHOD: Intraoperative and radiological data for patients who underwent ureteroscopic treatment of ureteric stones impaction over a 5-year period were reviewed retrospectively. Patients who had previous ureteroscopic treatment or strictures were excluded. RESULTS: Between January 2014 and May 2019, 1,340 patients presented as emergency renal colic secondary to ureteric stones. A total of 297 ureteroscopy procedures were performed for impacted calculi. The mean age was 53 years. The stricture rate was 3.3%. Analysis of radiological and surgical factors revealed that the degree of hydronephrosis, residual fragments and intraoperative ureteric injury were significant predictors for stricture formation (p = 0.018, 0.01 and 0.02, OR = 10, 47 and 1776, respectively). None of the other factors significantly predicted ureteric stricture formation. CONCLUSION: Our study found the presence of severe hydronephrosis, residual stone fragments after surgery and intraoperative ureteric injury are significant predictive factors for ureteric stricture formation. The high-risk patients should be monitored with routine postoperative renal ultrasound.

Identification of Tomato black ring virus from tomato plants grown in greenhouses in Saudi Arabia.

A survey was conducted in Al-Kharj governorate, Riyadh region to identify viruses causing variety of virus-like symptoms on tomato plants. A total of 135 samples were collected from symptomatic tomato plants. Symptoms included mottling, deformation, necrosis of leaves and fruits. Eighteen viruses were tested by DAS-ELISA. Tomato black ring virus (TBRV) was the virus of concern as it was not detected in Saudi Arabia before and was detected in 52.6% of the collected samples in this study. RT-PCR was used to confirm detection of TBRV and to sequence the amplified products to determine molecular characteristics of this virus. In the host range test study that was performed using a purified isolate of TBRV, sixteen out of the twenty two tested plants showed symptoms. Brassica oleracea was not infected by this virus. Gel electrophoreses (2% agarose) yielded fragments of 978 bp of coat protein gene of TBRV. Nucleotide sequences of purified RT-PCR products for three TBRV Saudi isolates were deposited in the GenBank with the following accession numbers MT274656, MT274657, and MT274658. These isolates of TBRV indicated a close Phylogenetic relationship of (99-100%) among themselves and with five isolates from Poland (95-98%) but a distant relationship of 85% with isolates from England and Lithuania deposited in the GenBank. This is the first report for detection and molecular characterization of TBRV infecting tomato plants in Saudi Arabia.

Combined Use of CytoSorb and ECMO in Patients with Severe Pneumogenic Sepsis.

BACKGROUND: High morbidity and mortality are frequently reported in intensive care patients suffering from severe sepsis with systemic inflammation. With the development of severe respiratory failure, extracorporeal membrane oxygenation (ECMO) is often required. In this study, cytokine adsorption therapy in combination with ECMO is applied in patients with acute respiratory distress syndrome (ARDS) due to severe pneumogenic sepsis. The efficacy of this therapy is evaluated compared with a historical cohort without hemoadsorption therapy. METHODS: Between January and May 2018, combined high-flow venovenous ECMO and CytoSorb therapy (CytoSorb filter connected to ECMO circuit) was applied in patients (n = 13) with pneumogenic sepsis and ARDS. These patients were prospectively included (CytoSorb group). Data from patients (n = 7) with pneumogenic sepsis and ECMO therapy were retrospectively analyzed (control group). RESULTS: All patients survived in the CytoSorb group, where the 30-day mortality rate reached 57% in the control group. After CytoSorb therapy, we instantly observed a significant reduction in procalcitonin (PCT) and C-reactive protein (CRP) levels compared with the control group. Within 48 hours, the initial high doses of catecholamine could be weaned off only in the CytoSorb group. CONCLUSIONS: Our results indicate that CytoSorb in combination with ECMO is an effective therapy to prevent escalation of sepsis with rapid weaning off high-dose catecholamine infusions and quick reduction in PCT and CRP levels. Optimal timing of immunomodulatory therapy and impact on ECMO-related inflammation still need to be furtherly investigated.

First Report of Tomato black ring virus (TBRV) on Tomato (Solanum lycopersicum) in Saudi Arabia.

Tomato is a popular vegetable crop that is cultivated worldwide. It is also one of the most important crops in Saudi Arabia. In 2017, the area in which tomato was grown in Saudi Arabia was estimated to be 13317 ha and produced 306389 tons. Al Kharj Governorate in Riyadh region contributes the highest production of greenhouse tomatoes in Saudi Arabia (Ministry of Env. WTR & AGRI., 2017). In fall 2015, striking virus-like symptoms (mottling, leaf rolling, yellowing, and deformation, black strip on the stem, cracking on fruits, deformation, mottling, and mummification with severe yield losses) were observed on greenhouse tomato plants in several farms in Al Kharj Governorate. Samples were collected within the period of fall 2015 and the summer of 2017. The collected samples were tested serologically using enzyme linked immunosorbent assay (ELISA) for identification of the causal agent(s) using kits and protocols from AC Diagnostics Inc (Fayetteville, Arkansas, UAS). Out of 18 common tomato viruses tested, 14 viruses were detected in tomato plants in the region. The greatest concern was the presence of Tomato black ring virus (TBRV) as this was the first detection in Saudi Arabia and displayed the highest frequency of detection among all other detected viruses. Seventy-one out of the 135 tested samples were positive for TBRV. To confirm the presence of TBRV in the infected tomato samples, total RNA was extracted from positive samples and tested by RT-PCR with the newly designed primer pair F-TBRV (5'-GCAAACCAACGCTCTATGTTGT-3')/R-TBRV (5'-AGAGCCAAACTGGAATGGTAGG-3') that is specific to the CP gene of TBRV. RT-PCR products of 978 bp in length were successfully obtained from the naturally infected tomato plants. One of the detected isolates was used to inoculate Chenopodium amaranticolor with the aim of obtaining a pure isolate from single local lesions that could be later used for propagation and maintenance in Nicotiana tabacum. A host range experiment was conducted using mechanical inoculation with the single-lesion isolate of TBRV on four replicates of 14 different plant species in parallel with healthy controls (Brunt et. al. 1996). Three weeks post-inoculation, varying reactions and symptoms ranging from local lesion to plant death, depending on host species, were observed on the tested plants (Supplementary Table 1). Host range results were largely similar to those reported in previous studies (Sneideris et al. 2012, and Rymelska et al. 2013). The presence of TBRV was confirmed both by ELISA and RT-PCR. Nucleotide sequences obtained from PCR products of selected samples were submitted to the GenBank and assigned the following accession numbers: MT274656, MT274657, and MT274658. Saudi isolates of TBRV were found to share 99-100% of their nucleotide sequences. They had the highest similarity of 98% with the Polish isolates (MG458221 and KX977561) and the lowest similarity of 85% with isolates from Lithuania (KF678369, and KF678370). To the best of our knowledge, this is the first report of occurrence of TBRV in Saudi Arabia. Since this virus is transmitted by seeds, it may have entered through imported seeds and spread in greenhouses through mechanical means. A survey of the different agricultural regions is encouraged to determine the incidence, distribution, and damage induced by this virus in Saudi Arabia.

Comparison of 'Excision and Primary Repair' with 'Bascom's Technique' in the Surgical Treatment of Pilonidal Sinus.

Introduction The management of the chronic pilonidal disease is variable and the principles of treatment are aimed to eradicate the sinus tract, promote wound healing, prevent disease recurrence, and improve the quality of life of the patient. This study aims to compare the effectiveness of excision and primary closure, and Bascom's technique in the management of pilonidal sinus disease. Methods  The study was performed at a tertiary hospital from April to October 2011. All patients with chronic pilonidal sinus were included in the study (n=60) and randomly allocated into Group A - undergoing excision and primary closure (n=30) and Group B - undergoing Bascom's repair. Comparative outcomes of interest were duration of hospital admission, post-operative pain, wound infection, wound-healing and disease recurrence.  Results The mean age of presentation was 24.18±5.6 years. A higher number of patients in Group A were discharged within 24 hours compared to Group B (p = 0.001). Group B had significantly less post-operative pain by the first postoperative week (p = 0.049). Group B had lower infection rates with clean wounds observed in 28 (93.3%) patients compared to 23 (76.7%) in Group A by the first postoperative week (p = 0.07). Recurrence rate during 12-week follow-up was observed in one (3.3%) patient in Group B, and five (16.7%) in Group A (p= 0.085). Conclusions Patients who underwent Bascom's operation had less postoperative pain, lower infection rates and disease recurrence, and better wound healing. Therefore, in our patient cohort, we conclude Bascom's repair appears to be superior to primary excision and repair in reducing patient morbidity.

Osteobastoma of the Talus: A case report and review of the literature.

Osteoblastoma is benign bone forming tumour with rare malignant transformation. The common locations include spine, proximal humerus and hip. It rarely affects the talus. A case of osteoblastoma of the talus in a 33-years old healthy male who presented to the foot and ankle clinic in October 2015 complaining of pain of the right ankle for 12 months following football injury is discussed.

Lucerne transient streak virus; a Recently Detected Virus Infecting Alfafa (Medicago sativa) in Central Saudi Arabia.

A survey was conducted to determine the status of Lucerne transient streak virus (LTSV) in three high-yielding alfalfa regions in central Saudi Arabia (Riyadh, Qassim, and Hail) during 2014. Three hundred and eight symptomatic alfalfa, and seven Sonchus oleraceus samples were collected. DAS-ELISA indicated that 59 of these samples were positive to LTSV. Two isolates of LTSV from each region were selected for molecular studies. RT-PCR confirmed the presence of LTSV in the selected samples using a specific primer pair. Percentage identity and homology tree comparisons revealed that all Saudi isolates were more closely related to each other but also closely related to the Canadian isolate-JQ782213 (97.1-97.6%) and the New Zealand isolate-U31286 (95.8-97.1%). Comparing Saudi isolates of LTSV with ten other sobemoviruses based on the coat protein gene sequences confirmed the distant relationship between them. Eleven out of fourteen plant species used in host range study were positive to LTSV. This is the first time to document that Trifolium alexandrinum, Nicotiana occidentalis, Chenopodium glaucum, and Lathyrus sativus are new host plant species for LTSV and that N. occidentalis being a good propagative host for it.

The immunomodulation potential of the synthetic derivatives of benzothiazoles: Implications in immune system disorders through in vitro and in silico studies.

Benzothiazole and its natural or synthetic derivatives have been used as precursors for several pharmacological agents for neuroprotective, anti-bacterial, and anti-allergic activities. The objective of the present study was to evaluate effects of benzothiazole analogs (compounds 1-26) for their immunomodulatory activities. Eight compounds (2, 4, 5, 8-10, 12, and 18) showed potent inhibitory activity on PHA-activated peripheral blood mononuclear cells (PBMCs) with IC50 ranging from 3.7 to 11.9 µM compared to that of the standard drug, prednisolone <1.5 µM. Some compounds (2, 4, 8, and 18) were also found to have potent inhibitory activities on the production of IL-2 on PHA/PMA-stimulated PBMCs with IC50 values ranging between <4.0 and 12.8 µM. The binding interaction of these compounds was performed through silico molecular docking. Compounds 2, 8, 9, and 10 significantly suppressed oxidative burst ROS production in phagocytes with IC50 values between <4.0 and 15.2 µM. The lipopolysaccharide (LPS)-induced nitrites in murine macrophages cell line J774 were found to be inhibited by compounds 4, 8, 9, and 18 at a concentration of 25 µg/mL by 56%, 91%, 58%, and 78%, respectively. Furthermore, compounds 5, 8, 12, and 18 showed significant (P<0.05) suppressive activity on Th-2 cytokine, interleukin 4 (IL-4) with an IC50 range of <4.0 to 40.3 µM. Interestingly compound 4 has shown a selective inhibitory activity on IL-2 and T cell proliferation (naïve T cell proliferation stage) rather than on IL-4 cytokine, while compound 12 displayed an interference with T-cell proliferation and IL-4 generation. Moreover compound 8 and 18 exert non-selective inhibition on both IL-2 and IL-4 cytokines, indicating a better interference with stage leading to humoral immune response and hence possible application in autoimmune diseases.

Immunosuppressive and hepatoprotective potential of Sarcococca saligna and its biomarker components.

Sarcococca saligna methanolic extract, fractions and isolated pure compounds saracocine (1), saracodine (2), pachyximine-A (3) and terminaline (4) were found to possess potent immunosuppressive activities. The fractions and compounds were tested in-vitro for their effects on human T-cell proliferation, and cytokine (IL-2) production. All the fractions, sub-fractions and purified compounds showed significant suppressive effect on IL-2 production in a dose-dependent manner. They also exhibited a suppressive effect on the phytohemagglutinin-stimulated T-cell proliferation. None of the extracts and purified compounds showed any cytotoxicity effects on the 3T3 mice fibroblast cell line. The crude extract, DCM fraction (pH9), DCM fractions (pH7) and one of the steroidal alkaloids (terminaline) were checked in-vivo for their hepato-protective potential against CCl4-induced liver injury. In in-vivo experiments, the basic and neutral DCM fractions and terminaline (4) significantly reduced inflammation in the liver. DCM fraction (pH9), DCM fractions (pH7) and compound 4 reduced the serum enzyme levels (ALT, AST, and ALP) down to control levels despite CCl4 treatment. They also reduced the CCl4-induced damaged area to almost zero as assessed by histopathology. The pale necrotic areas and mixed inflammatory infiltrate which are seen after CCl4 treatment were absent in the cases of basic, neutral fractions and terminaline treatment. These hepato-protective effects were better than the positive control silymarin. Our results suggest the therapeutic effect of S. saligna extract, fractions and bioactive steroidal alkaloids against CCl4-induced liver injury in vivo and their immunosuppressive function in vitro.