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.

PURPOSE: To identify risk factors for developing pressure ulcers (PUs) in the acute care period of traumatic spinal fracture patients with or without spinal cord injuries (SCIs). METHODS: Data were collected prospectively in participating the National Spinal column/Cord Injury Registry of Iran (NSCIR-IR) from individuals with traumatic spinal fractures with or without SCIs, inclusive of the hospital stay from admission to discharge. Trained nursing staff examined the patients for the presence of PUs every 8 h during their hospital stay. The presence and grade of PUs were assessed according to the European Pressure Ulcer Advisory Panel classification. In addition to PU, following data were also extracted from the NSCIR-IR datasets during the period of 2015 - 2021: age, sex, Glasgow coma scale score at admission, having SCIs, marital status, surgery for a spinal fracture, American Spinal Injury Association impairment scale (AIS), urinary incontinence, level of education, admitted center, length of stay in the intensive care unit (ICU), hypertension, respiratory diseases, consumption of cigarettes, diabetes mellitus and length of stay in the hospital. Logistic regression models were used to estimate the unadjusted and adjusted odds ratio (OR) with 95% confidence intervals (CI). RESULTS: Altogether 2785 participants with traumatic spinal fractures were included. Among them, 87 (3.1%) developed PU during their hospital stay and 392 (14.1%) had SCIs. In the SCI population, 63 (16.1%) developed PU during hospital stay. Univariate logistic regression for the whole sample showed that marital status, having SCIs, urinary incontinence, level of education, treating center, number of days in the ICU, age, and Glasgow coma scale score were significant predictors for PUs. However, further analysis by multiple logistic regression only revealed the significant risk factors to be the treating center, marital status, having SCIs, and the number of days in the ICU. For the subgroup of individuals with SCIs, marital status, AIS, urinary incontinence, level of education, the treating center, the number of days in the ICU and the number of days in the hospital were significant predictors for PUs by univariate analysis. After adjustment in the multivariate model, the treating center, marital status (singles vs. marrieds, OR = 3.06, 95% CI: 1.55 - 6.03, p = 0.001), and number of days in the ICU (OR = 1.06, 95% CI: 1.04 - 1.09, p < 0.001) maintained significance. CONCLUSIONS These data confirm that individuals with traumatic spinal fractures and SCIs, especially single young patients who suffer from urinary incontinence, grades A-D by AIS, prolonged ICU stay, and more extended hospitalization are at increased risk for PUs; as a result strategies to minimize PU development need further refinement.
Humans ; Spinal Fractures/etiology* ; Pressure Ulcer/complications* ; Iran/epidemiology* ; Spinal Cord Injuries/epidemiology* ; Risk Factors ; Spine ; Registries ; Urinary Incontinence/complications* ; Suppuration/complications*

Background: Spinal cord injury (SCI) is one of the most debilitating disorders throughout the world, causing persistent sensory-motor dysfunction, with no effective treatment. Oxidative stress and inflammatory responses play key roles in the secondary phase of SCI. Naringenin (NAR) is a natural flavonoid with known antiinflammatory and antioxidative properties. This study aims at evaluating the effects of intrathecal NAR administration on sensory-motor disability after SCI. Methods: Animals underwent a severe compression injury using an aneurysm clip. About 30 minutes after surgery, NAR was injected intrathecally at the doses of 5, 10, and 15 mM in 20 µL volumes. For the assessment of neuropathic pain and locomotor function, acetone drop, hot plate, inclined plane, and Basso, Beattie, Bresnahan tests were carried out weekly till day 28 post-SCI. Effects of NAR on matrix metalloproteinase (MMP)-2 and MMP-9 activity was appraised by gelatin zymography. Also, histopathological analyses and serum levels of glutathione (GSH), catalase and nitrite were measured in different groups. Results: NAR reduced neuropathic pain, improved locomotor function, and also attenuated SCI-induced weight loss weekly till day 28 post-SCI. Zymography analysis showed that NAR suppressed MMP-9 activity, whereas it increased that of MMP-2, indicating its anti-neuroinflammatory effects. Also, intrathecal NAR modified oxidative stress related markers GSH, catalase, and nitrite levels. Besides, the neuroprotective effect of NAR was corroborated through increased survival of sensory and motor neurons after SCI. Conclusions These results suggest intrathecal NAR as a promising candidate for medical therapeutics for SCI-induced sensory and motor dysfunction.

Objective: Recent studies have shown a possible association between vitamin D deficiency and the severity of primary dysmenorrhea. The present study aimed to investigate the effect of vitamin D supplementation on pain and systemic symptoms in patients with primary dysmenorrhea. Methods: This double-blind, randomized, placebo-controlled trial was conducted on female students aged 18 to 32 years with primary dysmenorrhea and vitamin D deficiency (25 [OH]D <30 ng/mL). The participants (n=116) received either 50,000 IU of vitamin D3 (cholecalciferol) or placebo capsules on a weekly basis for eight consecutive weeks. The outcomes were pain intensity (scored 0 to 10), number of days with pain, number of consumed pain-relief medications (per day), and severity of systemic symptoms (fatigue, headache, nausea/vomiting, and diarrhea; total score of 0 to 12). Results: Compared with baseline, our participants who received vitamin D experienced significant reductions in pain intensity (-1.0 and -1.5 score at weeks 4 and 8, P<0.001), the number of days with pain (-1.0 day at weeks 4 and 8, P<0.001), the number of consumed pain-relief medications (-1.0 at weeks 4 and 8, P<0.001), and systemic symptoms severity (-1.0 score at weeks 4 and 8, P<0.001). No significant improvements were observed in the placebo group in terms of these outcomes. Conclusion Vitamin D supplementation in women with primary dysmenorrhea and vitamin D deficiency could improve systemic symptoms and reduce pain intensity, the number of days with pain, and the need for consuming pain-relief medications.

Objective: Recent studies have shown a possible association between vitamin D deficiency and the severity of primary dysmenorrhea. The present study aimed to investigate the effect of vitamin D supplementation on pain and systemic symptoms in patients with primary dysmenorrhea. Methods: This double-blind, randomized, placebo-controlled trial was conducted on female students aged 18 to 32 years with primary dysmenorrhea and vitamin D deficiency (25 [OH]D <30 ng/mL). The participants (n=116) received either 50,000 IU of vitamin D3 (cholecalciferol) or placebo capsules on a weekly basis for eight consecutive weeks. The outcomes were pain intensity (scored 0 to 10), number of days with pain, number of consumed pain-relief medications (per day), and severity of systemic symptoms (fatigue, headache, nausea/vomiting, and diarrhea; total score of 0 to 12). Results: Compared with baseline, our participants who received vitamin D experienced significant reductions in pain intensity (-1.0 and -1.5 score at weeks 4 and 8, P<0.001), the number of days with pain (-1.0 day at weeks 4 and 8, P<0.001), the number of consumed pain-relief medications (-1.0 at weeks 4 and 8, P<0.001), and systemic symptoms severity (-1.0 score at weeks 4 and 8, P<0.001). No significant improvements were observed in the placebo group in terms of these outcomes. Conclusion Vitamin D supplementation in women with primary dysmenorrhea and vitamin D deficiency could improve systemic symptoms and reduce pain intensity, the number of days with pain, and the need for consuming pain-relief medications.

Vaginal atrophy is one of the most common menopausal complications and is often overlooked. There are various pharmacological and non-pharmacological treatment approaches to reduce vaginal atrophy; however, no comprehensive study on a convenient, affordable, inexpensive, and noninvasive treatment with fewer complications has been conducted so far. Thus, the current study aimed to provide a systematic review of pharmacological treatment for vaginal atrophy in postmenopausal women in Iran. In this systematic review, all Iranian articles published in Persian or English during 2009 to 2019 were collected and analyzed by searching the Scopus, PubMed, Web of Science, Magiran, Iranian Registry of Clinical Trials (IRCT), and Cochrane Library databases. The inclusion criteria were clinical trials for vaginal atrophy and menopause. Based on the selection criteria, articles with a Jadad scale score of 3 and above were included in the study and qualitatively analyzed. Overall, 15 clinical trials met the inclusion criteria. In total, 12 articles examined the efficacy of pharmacological treatments (including three herbal medicines, three vitamins and dietary supplements, and two chemical drugs) in treating vaginal atrophy in postmenopausal women. Various types of medication have been used to improve vaginal atrophy, and effective treatments include licorice, chamomile, royal jelly, vitamin E, vitamin D, hyaluronic acid, and Vagifem; however, the results of studies on fennel have been inconsistent. However, considering the small number of studies reviewed, further studies with a stronger methodology are needed to confirm the efficacy of these medications.

OBJECTIVES:: Investigating the survival of patients with cancer is vitally necessary for controlling the disease and for assessing treatment methods. This study aimed to compare various statistical models of survival and to determine the survival rate and its related factors among patients suffering from lung cancer. METHODS:: In this retrospective cohort, the cumulative survival rate, median survival time, and factors associated with the survival of lung cancer patients were estimated using Cox, Weibull, exponential, and Gompertz regression models. Kaplan-Meier tables and the log-rank test were also used to analyze the survival of patients in different subgroups. RESULTS:: Of 102 patients with lung cancer, 74.5% were male. During the follow-up period, 80.4% died. The incidence rate of death among patients was estimated as 3.9 (95% confidence [CI], 3.1 to 4.8) per 100 person-months. The 5-year survival rate for all patients, males, females, patients with non-small cell lung carcinoma (NSCLC), and patients with small cell lung carcinoma (SCLC) was 17%, 13%, 29%, 21%, and 0%, respectively. The median survival time for all patients, males, females, those with NSCLC, and those with SCLC was 12.7 months, 12.0 months, 16.0 months, 16.0 months, and 6.0 months, respectively. Multivariate analyses indicated that the hazard ratios (95% CIs) for male sex, age, and SCLC were 0.56 (0.33 to 0.93), 1.03 (1.01 to 1.05), and 2.91 (1.71 to 4.95), respectively. CONCLUSIONS:: Our results showed that the exponential model was the most precise. This model identified age, sex, and type of cancer as factors that predicted survival in patients with lung cancer.
Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Incidence ; Iran ; Lung Neoplasms ; Lung ; Male ; Models, Statistical ; Multivariate Analysis ; Retrospective Studies ; Small Cell Lung Carcinoma ; Survival Rate

OBJECTIVES: : Investigating the survival of patients with cancer is vitally necessary for controlling the disease and for assessing treatment methods. This study aimed to compare various statistical models of survival and to determine the survival rate and its related factors among patients suffering from lung cancer. METHODS: : In this retrospective cohort, the cumulative survival rate, median survival time, and factors associated with the survival of lung cancer patients were estimated using Cox, Weibull, exponential, and Gompertz regression models. Kaplan-Meier tables and the log-rank test were also used to analyze the survival of patients in different subgroups. RESULTS: : Of 102 patients with lung cancer, 74.5% were male. During the follow-up period, 80.4% died. The incidence rate of death among patients was estimated as 3.9 (95% confidence [CI], 3.1 to 4.8) per 100 person-months. The 5-year survival rate for all patients, males, females, patients with non-small cell lung carcinoma (NSCLC), and patients with small cell lung carcinoma (SCLC) was 17%, 13%, 29%, 21%, and 0%, respectively. The median survival time for all patients, males, females, those with NSCLC, and those with SCLC was 12.7 months, 12.0 months, 16.0 months, 16.0 months, and 6.0 months, respectively. Multivariate analyses indicated that the hazard ratios (95% CIs) for male sex, age, and SCLC were 0.56 (0.33 to 0.93), 1.03 (1.01 to 1.05), and 2.91 (1.71 to 4.95), respectively. CONCLUSIONS : Our results showed that the exponential model was the most precise. This model identified age, sex, and type of cancer as factors that predicted survival in patients with lung cancer.

Objective: To investigate Echinococcus (E.) granulosus genotypes as the causative agents of hydatidosis in humans in the southwest of Iran (Khuzestan province). Methods: In this study, isolates of 80 archived human paraffin embedded hydatid cysts were collected from pathology laboratories in Ahvaz city, Khuzestan province. DNA was extracted and examined by nested-PCR of ribosomal DNA (rDNA) internal transcribed spacer 1 (ITS1), and PCR-RFLP. In addition, the sequences of fragments of genes coding for Cox space1 and NADH dehydrogenase 1 (ND1) were also examined. Results: Of the 80 paraffin samples, 44 (55.0%) were from the liver, 27 (33.8%) from the lung, and the rest from other organs. The amplified hydatid genomic DNA showed that the cysts were E. granulosus strains. The results of PCR-RFLP and sequencing analysis revealed the presence of G1 genotype (sheep strain) in all human isolates. Furthermore, no camel strain (G6) was detected among all samples in the regions studied. Conclusions: The molecular findings indicate that the predominant genotype involved in E. granulosus transmission in southwest of Iran is the common sheep strain (G1), which occurs in human populations. These results may have important implications for hydatid disease control in the studied areas.

Objective To evaluate the efficacy of combined ABZ and PZQ and their solid lipid nanoparticles in chemoprophylaxis of cystic echinococcosis (CE). Methods ABZ and PZQ loaded solid lipid nanoparticles (SLNs) were prepared by high shear homogenization and microemulsion congealing techniques with some minor modification. Nanoparticles average size, polydispersity index (PDI), and particle size distribution were determined by scanning electron microscopy (SEM) and photon correlation spectroscopy. Forty females BALB/c were experimentally infected by protoscoleces (PSC) and randomly divided into four equal groups of 10 mice. After the end of the 3 months treatment period and 2 months rest, mice were sacrificed and the peritoneal cavity was opened for removal, counting, measuring, and histological analysis of hydatid cyst. Results The results indicated that ABZ and PZQ chemoprophylaxis treatment reduced the wet weight and size of developed cysts 77.3% and 79%, respectively. The corresponding result for the ABZ and PZQ loaded SLNs was 83% and 85%, respectively. Conclusions This study for the first time demonstrated that ABZ and PZQ loaded SLNs is superior to free ABZ and PZQ for the chemoprophylaxis of CE in mice.