Beneficial effect of metformin on tolerance to analgesic effects of sodium salicylate in male rats.

Background: Tolerance to the analgesic effects of opioids and non-steroidal anti-inflammatory drugs (NSAIDs) is a major concern for relieving pain. Thus, it is highly valuable to find new pharmacological strategies for prolonged therapeutic procedures. Biguanide-type drugs such as metformin (MET) are effective for neuroprotection and can be beneficial for addressing opioid tolerance in the treatment of chronic pain. It has been proposed that analgesic tolerance to NSAIDs is mediated by the endogenous opioid system. According to the cross-tolerance between NSAIDs, especially sodium salicylate (SS), and opiates, especially morphine, the objective of this study was to investigate whether MET administration can reduce tolerance to the anti-nociceptive effects of SS. Methods: Fifty-six male Wistar rats were used in this research (weight 200-250 g). For induction of tolerance, SS (300 mg/kg) was injected intraperitoneally for 7 days. During the examination period, animals received MET at doses of 50, 75, or 100 mg/kg for 7 days to evaluate the development of tolerance to the analgesic effect of SS. The hot plate test was used to evaluate the drugs' anti-nociceptive properties. Results: Salicylate injection significantly increased hot plate latency as compared to the control group, but the total analgesic effect of co-treatment with SS + Met50 was stronger than the SS group. Furthermore, the effect of this combination undergoes less analgesic tolerance over time. Conclusions: It can be concluded that MET can reduce the analgesic tolerance that is induced by repeated intraperitoneal injections of SS in Wister rats.

Pain-Insomnia-Depression Syndrome: Triangular Relationships, Pathobiological Correlations, Current Treatment Modalities, and Future Direction.

Pain-insomnia-depression syndrome (PIDS) is a complex triad of chronic pain, insomnia, and depression that has profound effects on an individual's quality of life and mental health. The pathobiological context of PIDS involves complex neurobiological and physiological mechanisms, including alterations in neurotransmitter systems and impaired pain processing pathways. The first-line therapeutic approaches for the treatment of chronic pain, depression, and insomnia are a combination of pharmacological and non-pharmacological therapies. In cases where patients do not respond adequately to these treatments, additional interventions such as deep brain stimulation (DBS) may be required. Despite advances in understanding and treatment, there are still gaps in knowledge that need to be addressed. To improve our understanding, future research should focus on conducting longitudinal studies to uncover temporal associations, identify biomarkers and genetic markers associated with PIDS, examine the influence of psychosocial factors on treatment responses, and develop innovative interventions that address the complex nature of PIDS. The aim of this study is to provide a comprehensive overview of these components and to discuss their underlying pathobiological relationships.

Postpartum Septic Pelvic Thrombophlebitis in a Tertiary Maternity Hospital in Dubai, UAE.

Septic pelvic thrombophlebitis (SPT) is a well-known condition, yet it remains a rare postpartum complication. It can be divided into two types: deep septic pelvic thrombophlebitis (DSPT) and ovarian vein thrombosis (OVT). In this case series, we present three cases diagnosed with ovarian vein thrombosis that were managed in our tertiary care hospital, Latifa Women and Children Hospital (LWCH), in Dubai, UAE. It is a 440-bed public tertiary care center that specializes in maternal and neonatal services, with a range of 3500 to 4000 deliveries per year. The three cases represent the total number diagnosed with this condition in the period between 2018 and 2022 among the total obstetric population during this period. The three cases developed a fever in the postpartum period, which for several days did not respond to the standard antibiotics used for endometritis. Two cases were following a cesarean section, and the third case was following vaginal delivery complicated with severe postpartum hemorrhage and hysterectomy. The clinical suspicion and awareness of the condition paved the way to reach the proper diagnosis and initiate the therapeutic dose of anticoagulants, along with broad-spectrum antibiotics, in a timely manner. The prompt diagnosis with early intervention led to optimal patient outcomes and prevented the morbidity and mortality associated with this condition.

Perinatal anxiety and depression amidst the COVID-19 pandemic in Dubai, United Arab Emirates.

BACKGROUND: Pregnancy and COVID-19 increase the risk of mental health conditions. The stress of pregnancy, childbirth, and uncertainty about the global pandemic has negatively affected the obstetrical population. OBJECTIVE: This study aimed to investigate the effects of the COVID-19 pandemic in terms of anxiety and depression in antenatal and postnatal mothers. STUDY DESIGN: This was a cross-sectional observational study conducted at Dubai Hospital, United Arab Emirates, evaluating depression and anxiety (point prevalence) with the Edinburgh Postnatal Depression Scale and Generalized Anxiety Disorder-7 scale. RESULTS: Of the 784 women approached, 438 consented to participate in our survey; 43.6% of the women screened positive for depression by the Edinburgh Postnatal Depression Scale (with a cutoff score ≥10), and 42% had a Generalized Anxiety Disorder-7 score of ≥5, indicating anxiety. Both anxiety and depression were found in 32.4% of the women; 7.5% had considered self-harm in the last 14 days, and 15% had COVID-19 during the current pregnancy. The 11.87% who had COVID-19, but before the pregnancy, had higher mean Edinburgh Postnatal Depression Scale and Generalized Anxiety Disorder-7 scores than others. Surprisingly, the women who had COVID-19 during pregnancy had statistically significantly (P<.05) lower Edinburgh Postnatal Depression Scale and Generalized Anxiety Disorder-7 scores. University graduates had significantly (P<.05) higher Edinburgh Postnatal Depression Scale and Generalized Anxiety Disorder-7 scores. Women of Middle Eastern ethnicity (50% positive for depression and 48.5% for anxiety) were more prone to depression and anxiety compared with South Asian (29% positive for depression and 25.2% for anxiety) and African women (39.6% positive for depression and 43.4% for anxiety). There was no statistically significant difference between antenatal and postnatal patients in the prevalence of anxiety or depression. CONCLUSION: The COVID-19 pandemic is associated with an increase in depression and anxiety in pregnant and postnatal women. Women who were more concerned about the effects of the pandemic had higher mean Edinburgh Postnatal Depression Scale and Generalized Anxiety Disorder-7 scores. Additional psychological support for women is necessary during the pandemic for maternal perinatal well-being.

Comparative investigation of analgesic tolerance to taurine, sodium salicylate and morphine: Involvement of peripheral muscarinic receptors.

Nowadays various analgesic medications are used for the management of acute and chronic pain. Among these opioid and non-steroidal anti-inflammatory drugs stand in the first line of therapy, however, prolonged administration of these substance is generally challenged by development of analgesic tolerance in patients. Therefore, it is highly valuable to find new pharmacological strategies for prolonged therapeutic procedures. In this respect, Taurine, a free amino acid, has been shown to induce significant analgesia at both spinal and peripheral levels through cholinergic mechanisms. In the present study, we used hot-plate analgesic test to investigate how taurine either as a single medication or in combination with sodium salicylate and morphine may affect both acute response to pain and development of analgesic tolerance. The effect of taurine was also tested on morphine withdrawal syndrome. Hyoscine butyl bromide was used to assess the role of muscarinic receptors in taurine-mediated effects. Finally, biochemical assay was done to reveal how the activity of brain acetylcholinesterase may change in relation with muscarinic receptor activity. Results indicated that acute administration of taurine-sodium salicylate combination causes more potent analgesia compared to the use of tau (but not SS alone) and this seems to be mediated via activity of muscarinic receptors in peripheral nervous system. Furthermore, the effect of this combination undergoes less analgesic tolerance during time. Combination of taurine and morphine is an effective strategy to attenuate both morphine analgesic tolerance and dependence and this also seems to depend on activity of muscarinic receptors, however through differential cellular mechanisms.

Corneal sustained delivery of hyaluronic acid from nanofiber-containing ring-implanted contact lens.

Dry eye syndrome, as a persist corneal epithelial defect (PED), is an inconvenient ocular disorder that is generally treated by high-dosage, conventional eye drops. Addressing low efficacy and rather restricted bioavailability of the conventional eye drops, drug-eluting contact lenses (CLs) are widely used as alternatives in ophthalmic drug delivery applications. In the present study, a nanofiber-containing ring implant poly (vinyl alcohol) (PVA) hydrogel is designed as a carrier for hyaluronic acid (HA) delivery. hyaluronic acid is physically encapsulated in a nanofiber-containing ring-shaped hydrogel with a 2 mm width that is implanted in the final CLs hydrogel. The designed CL has 59% porosity, 275% swelling ratio and undergoes no weight loss at physiological conditions in14 days. In-vitro release studies were performed on the CLs with and without nanofibers. The results showed that nanofiber incorporation in the designed CL was highly influential in decreasing burst release and supported sustained release of HA over 14 days. In addition, nanofiber incorporation in the designed system strengthened the lens, and the young modulus of the PVA hydrogel increased from 6 to 10 kPa. Cell viability study also revealed no cell cytotoxicity and cell attachment. Overall, the study demonstrated the effective role of nanofibers in the physical strengthening of the CL. Also, the designed system holds promise as a potential candidate for HA delivery over an extended period for treating dry eye syndrome.

Vitamin B12 administration prevents ethanol-induced learning and memory impairment through re-establishment of the brain oxidant/antioxidant balance, enhancement of BDNF and suppression of GFAP.

There are growing evidence indicating that the adolescent brain is persistently affected by the use of psychostimulant agents. In this regard, alcohol drinking has become rather common among the adolescents in many societies during the last decade. It is currently well known that long-term ethanol exposure deteriorates various cognitive functions such as learning and memory. Mechanistically, these adverse effects have been shown to be mediated by oxidative damage to central nervous system. On the other hand, Vit-B12 is known to improve cognitive performance by suppression of oxidative parameters. Thus, in the present study we aimed to test whether treatment by Vit-B12 could prevent ethanol-induced complications in mice using behavioral and biochemical methods. Different groups of male Syrian mice received ethanol, ethanol+Vit-B12, Vit-B12 alone, or saline during adolescence and then learning and memory functions were assessed by Morris water maze (MWM) and Passive Avoidance (PA) tests. Finally, mice were sacrificed for measurement of biochemical factors. Results indicated that, adolescent ethanol intake impairs learning and memory function through exacerbation of oxidative stress and Vit-B12 treatment improves these complications by re-establishment of oxidant/anti-oxidant balance in CNS. Moreover, we found that Vit-B12 prevents ethanol-induced reduction of BDNF and enhancement of GFAP and acetylcholinesterase (AChE) activity. In conclusion, it seems that Vit-B12 supplementation could be used as an effective therapeutic strategy to prevent learning and memory defects induced by chronic alcohol intake during adolescence.

Crocin, the main active saffron (Crocus sativus L.) constituent, as a potential candidate to prevent anxiety and depressive-like behaviors induced by unpredictable chronic mild stress.

INTRODUCTION: Saffron, the dried stigmas of Crocus sativus L. is a famous and high-value agricultural product of Iran exclusively used for cooking purpose and well known to treat mood and cognition disorder with antioxidant and anti-inflammatory activities. However, the majority of medicinal properties of saffron are associated with its main component named Crocin. Several evidence-based studies confirmed the strong positive correlation between stress hormones, and depression. The main aim of the present study is to determine the potential antidepressant effects of crocin, saffron's constitute, in unpredictable chronic mild stress (UCMS) induced anxiety and depression in rats. MATERIALS AND METHODS: The rats were treated as 1) Vehicle with saline, 2) UCMS, 3-5) UCMS- Crocin 10, 20, and 30 mg/kg by oral gavage, 6) Vehicle with Crocin 30 mg/kg by oral gavage. Male Wistar Rats were subjected to UCMS for a total of 4 weeks. During 4 weeks, they received seven training trials. After behavioral tests, the rat brain sections were collected to examine inflammation and oxidative stress damage criteria. RESULTS: Serum corticosterone levels, cortical malondialdehyde (MDA), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were increased in rats exposed to UCMS, while UCMS decreased IL-10 superoxide dismutase (SOD), Catalase (CAT, and thiol. In addition, UCMS decreased brain-derived neurotrophic factor (BDNF) level in cortical tissues. Crocin improved the behaviors of the UCMS rats in the open field (OF, elevated plus maze (EPM), and forced swimming (FS) tests and reversed the effects of UCMS in all measured parameters. CONCLUSION: Crocin improved UCMS -induced anxiety and depression through decreasing brain oxidative stress, inflammatory mediators, and corticosterone serum levels.

The Clinical Outcome of Laparoscopic Surgery for Endometriosis on Pain, Ovarian Reserve, and Cancer Antigen 125 (CA-125): A Cohort Study.

BACKGROUND: Endometriosis is an important cause of chronic pain and infertility. Surgery is considered the gold standard for diagnosis and treatment. In this study, we aim to describe the clinical outcomes of women who undergo laparoscopic surgery for endometriosis. MATERIALS AND METHODS: In this cohort study, a total of 174 women who referred to Farmaniyeh Hospital, Tehran, Iran from August 2015 to December 2017 with surgical diagnoses of endometriosis stages III and IV enrolled. The participants' demographic, gynaecological, and clinical characteristics were recorded and they were asked to use a numeric rating scale (NRS) to record their severity of pain before and three months after surgery. Blood samples were also taken from the patients before and three months after surgery for measurement of serum levels of anti-Müllerian hormone (AMH) and cancer antigen 125 (CA-125). Data were analysed using SPSS version 21. RESULTS: The patients had a mean age of 34.86 ± 6.47 years, 60.9% were married, and 49.4% were housewives. The primary indication for surgery was pain (68.4%), followed by both pain and infertility in the remainder of patients. Types of endometriotic lesions included endometrioma (19%), deep infiltrating endometriosis (DIE, 3.4%), and both endometrioma and DIE (77.6%). There was a reduction in pain from 6.79 ± 2.19 before surgery to 1.48 ± 1.68 after surgery; serum AMH levels reduced from 2.80 ± 1.86 ng/mL to 1.76 ± 1.40 ng/mL and CA125 reduced from 257.06 ± 220.25 U/mL to 23.27 ± 23.25 U/mL (all P<0.001). Of the 21.2% who experienced recurrence, 13.5% underwent additional surgery. The total additional surgery rate was 2.8%. Of the 55 patients with infertility, 78.1% became pregnant after surgery, 54.5% of which was spontaneous. CONCLUSION: Surgical treatment of endometriosis had a favourable effect on the patients' pain and inflammation and resolved the patients' infertility with a minimal need for additional surgery.

A novel biosurfactant producing Kocuria rosea ABR6 as potential strain in oil sludge recovery and lubrication.

Biosurfactants are amphiphilic molecules composed of a hydrophilic and hydrophobic moiety and had the ability to penetrate into different phases to reduce the surface tension. This features caused to oil recovery, lubrication and facilities of crude oil in pipeline. In current research Biosurfactant-producing strain was isolated from the storage tanks of the Isfahan Oil Refining Company in Iran, and screened by oil expansion test, droplet collapse, and surface tension reduction measurement. Hydrocarbon recovery from crude oil sludge was measured under constant conditions. The effect of factoring biosource lubrication on crude oil in pipelines was investigated in vitro. Also, the optimization of biosurfactant production in different conditions was measured as a single factor and using Response Surface Method (RSM). The best biosurfactant-producing bacterium was identified as Kocuria rosea ABR6, and its sequence was registered in the gene bank with access number of MK100469. Chemical analysis proved that the produced biosurfactant was a lipopeptide. 7% of crude oil was recovered from petroleum sludge by biosurfactant obtained from Kocuria rosea ABR6. Also, the speed of crude oil transfer in pipelines was upgraded as it could be said that for a certain distance the transfer time reduced from 64 to 35 s. The highest biosurfactant production was measured at pH 9, aeration rate of 120 rpm and 96 h after incubation. The use of biosurfactants produced by Kocuria rosea ABR6 is recommended to remove oil sludge and lubricate oil in pipelines recommended in the oil industry.

An Overview of Engineered Hydrogel-Based Biomaterials for Improved ß-Cell Survival and Insulin Secretion.

Islet transplantation provides a promising strategy in treating type 1 diabetes as an autoimmune disease, in which damaged ß-cells are replaced with new islets in a minimally invasive procedure. Although islet transplantation avoids the complications associated with whole pancreas transplantations, its clinical applications maintain significant drawbacks, including long-term immunosuppression, a lack of compatible donors, and blood-mediated inflammatory responses. Biomaterial-assisted islet transplantation is an emerging technology that embeds desired cells into biomaterials, which are then directly transplanted into the patient, overcoming the aforementioned challenges. Among various biomaterials, hydrogels are the preferred biomaterial of choice in these transplants due to their ECM-like structure and tunable properties. This review aims to present a comprehensive overview of hydrogel-based biomaterials that are engineered for encapsulation of insulin-secreting cells, focusing on new hydrogel design and modification strategies to improve ß-cell viability, decrease inflammatory responses, and enhance insulin secretion. We will discuss the current status of clinical studies using therapeutic bioengineering hydrogels in insulin release and prospective approaches.

Preparation of Nanoparticle-Containing Ring-Implanted Poly(Vinyl Alcohol) Contact Lens for Sustained Release of Hyaluronic Acid.

Here, a novel ring-implanted poly vinyl alcohol (PVA) contact lens (CL) is fabricated and evaluated as a therapeutic CL with potential of sustained release of hyaluronic acid (HA). HA is loaded on chitosan (CS) nanoparticles (NPs) and then the HA-loaded NPs are dispersed in a ring shape PVA hydrogel which is implanted in the final PVA CL. Results show that HA is successfully loaded on NPs (520 ± 18 nm) with loading efficacy of 87% and loading capacity of 50%. The CL hydrogel has a 275% swelling ratio, no degradation during 14 days, 97% light transmittance, and desirable rheological stability under physiological shear force. The release data show a sustained release for HA from the ring implanted CL up to 14 days. The cellular study reveals no corneal epithelial cell cytotoxicity and cell attachment on the CL. The study demonstrates the successful application of the ring-implanted CL to sustain the delivery of HA for treating the dry eye syndrome.

Introducing the risk aggregation problem to aquifers exposed to impacts of anthropogenic and geogenic origins on a modular basis using 'risk cells'.

Proof-of-concept is presented in this paper to a methodology formulated for indexing risks to groundwater aquifers exposed to impacts of diffuse contaminations from anthropogenic and geogenic origins. The methodology is for mapping/indexing, which refers to relative values but not their absolute values. The innovations include: (i) making use of the Origins-Source-Pathways-Receptors-Consequences (OSPRC) framework; and (ii) dividing a study area into modular Risk (OSPRC) Cells to capture their idiosyncrasies with different origins. Field measurements are often sparse and comprise pollutants and water table, which are often costly; whereas supplementary data are general-purpose data, which are widely available. Risk mapping for each OSPRC cell is processed by dividing a study area into pixels and for each pixel, the risk from both anthropogenic and geogenic origins are indexed by using algorithms related to: (i) Vulnerability Indices (VI), which identify the potential for risk exposures at each pixel; and (ii) velocity gradient, which expresses the potency to risk exposures across the risk cell. The paper uses DRASTIC for anthropogenic VI but introduces a new framework for geogenic VI. The methodology has a generic architecture and is flexible to modularise risks involving any idiosyncrasies in a generic way in any site exposed to environmental pollution risks. Its application to a real study area provides evidence for the proof-of-concept for the methodology by a set of results that are fit-for-purpose and provides an insight into the study area together with the identification of its hotspots.

Health risk assessment of heavy metal intake due to fish consumption in the Sistan region, Iran.

The heavy metal (Pb, Cd, Cr, and Ni) content of a fish species consumed by the Sistan population and its associated health risk factors were investigated. The mean concentrations of Pb, Cd, and Cr were slightly higher than the standard levels. The Ni content of fish was below the maximum guideline proposed by the US Food and Drug Administration (USFDA). The average estimated weekly intake was significantly below the provisional tolerable intake based on the FAO and WHO standards for all studied metals. The target hazard quotients (THQ) of all metals were below 1, showing an absence of health hazard for the population of Sistan. The combined target hazard quotient for the considered metals was 26.94 × 10-3. The cancer risk factor for Pb (1.57 × 10-7) was below the acceptable lifetime carcinogenic risk (10-5). The results of this study reveal an almost safe level of Pb, Cd, Cr, and Ni contents in the fish consumed by the Sistan population. Graphical abstract ᅟ.

Fertility outcome after laparoscopic treatment of advanced endometriosis in two groups of infertile patients with and without ovarian endometrioma.

OBJECTIVE: To evaluate the result of laparoscopic endometrioma excision in fertility outcome of advanced endometriosis patients. STUDY DESIGN: The study was designated as historical cohort, in a private referral center of advance laparoscopy. 111 infertile patients, diagnosed as endometriosis, were divided in two groups: DIE (deep infiltrative endometriosis) and endometrioma (case group), and patients with only DIE (without endometrioma ((control group). All patients underwent global laparoscopic resection of DIE lesion (both groups) and laparoscopic excisional cystectomy of endometrioma (case groups). Patients were followed for fertility outcomes and data were analyzed by Kaplan-Meier test and COX regression using SPSS software. RESULTS: After adjusting covariates, the Kaplan-Meier analysis of cumulative pregnancy rates (CPR) did not show any statistical significance between cases (35.6%) and controls (39.5%) (Log-rank P-value=0.959). The COX regression analysis of covariates showed there is no significant relationship between cystectomy and fertility outcome. It showed statistical significance effect of age (hazard ratio [HR]=0.772), years of infertility (HR=0.224), and previous endometrioma surgery (HR=0.180), on fertility chance. CONCLUSION: In advanced endometriosis with DIE and infertility, fine excision and stripping of the endometrioma along with radical resection of DIE improves fecundity without any significant adverse effect in comparison with patients with intact ovaries.

Premenstrual syndrome and quality of life in Iranian medical students.

PURPOSE OF STUDY: The purpose of this research was to investigate the prevalence of premenstrual syndrome (PMS) in medical students and to evaluate the hypothesis that PMS may result in a decrease in quality of life. METHODS: In a cross-sectional study, 142 female medical students who study at Urmia University of Medical Sciences were included. The data were compiled using a PMS questionnaire based on the fourth version (DSM-IV) criteria, the questionnaire of "Premenstrual Syndrome Scale" as well as the "World Health Organization's Quality of Life (WHOQOL-BREF)" questionnaire. FINDINGS: In total, 56 out of 142 (39.4%) female medical students met the DSM-IV criteria for PMS. In the PMS group, more than half of the girls, i.e. 60.6% had mild, 25.1% had moderate and 14.2% had severe PMS. PMS was found to be significantly high in students who have positive history of PMS in their first degree relatives and who have used drugs to relieve PMS symptoms (P<0.05). Life quality score was low in more than half of the medical students, especially in psychological and social components (P>0.05). However, the quality of life score means in mental health (P=0.02) and environmental health (P=0.002) decreases as the PMS score average increases. CONCLUSION: The results of premenstrual syndrome prevalence and their severity suggest that PMS is common in medical students and this adversely affects some domains of the quality of life. Improving the life quality of female medical students needs some interventions related to the PMS and also other interventions not related to PMS.

Eutopic and ectopic stromal cells from patients with endometriosis exhibit differential invasive, adhesive, and proliferative behavior.

OBJECTIVE: To study immunophenotype, differential proliferation capacity, invasiveness, adhesion, and cytokine production in ectopic and eutopic endometrial stromal cells (EESCs and EuESCs) from patients with endometriosis. DESIGN: In vitro study. SETTING: Academic research center. PATIENT(S): Patients with ovarian endometriosis (endometrioma) and nonendometriotic controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): EESCs and EuESCs from 25 patients with endometrioma and ESCs from 20 nonendometriotic controls (CESCs) were isolated, and their immunophenotype, proliferation, invasion, adhesion, and cytokine production were assessed and compared. RESULT(S): Isolated ESCs from all three sources expressed markers specific for cells of mesenchymal origin but were negative for hematopoietic markers. EESCs exhibited a significantly lower proliferation rate in fibronectin-coated plates and less invasive capacity compared with CESCs or EuESCs. Among all stromal cell groups studied, EuESCs showed the highest invasive behavior. EESCs adhered more firmly to extracellular matrix than EuESCs or CESCs in all time intervals examined. The levels of interleukin (IL) -6 and IL-8 production by EESCs were significantly higher compared with those of EuESCs or CESCs. CONCLUSION(S): The results of the present study demonstrated that retrograde menstruation alone does not account for the pathogenesis of endometriosis as eutopic and ectopic counterparts of ESCs from patients with endometriosis exhibit differential invasive, adhesive, and proliferative behavior.