Combination of losartan with pirfenidone: a protective anti-fibrotic against pulmonary fibrosis induced by bleomycin in rats.

Pirfenidone (PFD), one acceptable medication for treating idiopathic pulmonary fibrosis (IPF), is not well tolerated by patients at full doses. Hence, employing of some approaches such as combination therapy may be applicable for increasing therapeutic efficacy of PFD. Losartan (LOS), an angiotensin II receptor antagonist, could be a suitable candidate for combination therapy because of its stabilizing effect on the pulmonary function of IPF patients. Therefore, this study aimed to investigate the effects of LOS in combination with PFD on bleomycin (BLM)-induced lung fibrosis in rats. BLM-exposed rats were treated with LOS alone or in combination with PFD. The edema, pathological changes, level of transforming growth factor-ß (TGF-ß1), collagen content, and oxidative stress parameters were assessed in the lung tissues. Following BLM exposure, the inflammatory response, collagen levels, and antioxidant markers in rat lung tissues were significantly improved by PFD, and these effects were improved by combination with LOS. The findings of this in vivo study suggest that the combined administration of PFD and LOS may provide more potent protection against IPF than single therapy through boosting its anti-inflammatory, anti-fibrotic, and anti-oxidant effects. These results hold promise in developing a more effective therapeutic strategy for treating of lung fibrosis.

Lung molecular and histological changes in type 2 diabetic rats and its improvement by high-intensity interval training.

BACKGROUND: Type 2 diabetes (T2D) leads to serious respiratory problems. This study investigated the effectiveness of high-intensity interval training (HIIT) on T2D-induced lung injuries at histopathological and molecular levels. METHODS: Forty-eight male Wistar rats were randomly allocated into control (CTL), Diabetes (Db), exercise (Ex), and Diabetes + exercise (Db + Ex) groups. T2D was induced by a high-fat diet plus (35 mg/kg) of streptozotocin (STZ) administration. Rats in Ex and Db + Ex performed HIIT for eight weeks. Tumor necrosis factor-alpha (TNFα), Interleukin 10 (IL-10), BAX, Bcl2, Lecithin, Sphingomyelin (SPM) and Surfactant protein D (SPD) levels were measured in the bronchoalveolar lavage fluid (BALF) and malondialdehyde (MDA) and total antioxidant capacity (TAC) levels were measured in lung tissue. Lung histopathological alterations were assessed by using H&E and trichrome mason staining. RESULTS: Diabetes was significantly associated with imbalance in pro/anti-inflammatory, pro/anti-apoptosis and redox systems, and reduced the SPD, lecithin sphingomyelin and alveolar number. Performing HIIT by diabetic animals increased Bcl2 (P < 0.05) and IL10 (P < 0.01) levels as well as surfactants components and TAC (P < 0.05) but decreased fasting blood glucose (P < 0.001), TNFα (P < 0.05), BAX (P < 0.05) and BAX/Bcl2 (P < 0.001) levels as well as MDA (P < 0.01) and MDA/TAC (P < 0.01) compared to the diabetic group. Furthermore, lung injury and fibrosis scores were increased by T2D and recovered in presence of HIIT. CONCLUSION: These findings suggested that the attenuating effect of HIIT on diabetic lung injury mediated by reducing blood sugar, inflammation, oxidative stress, and apoptosis as well as improving pulmonary surfactants components.

Sodium hydrogen sulfide may not protect the kidney against ischemia/reperfusion damage in male and female rats.

Background and purpose: Renal ischemia/reperfusion (IR) injury is a pathologic phenomenon that caused to increase risk of mortality. The main objective of this study was to investigate the effect of sodium hydrogen sulfide (NaHS) on renal IR injury in male and female rats. Experimental approach: Fifty-eight male and female rats were randomized into 4 groups of control, sham, IR, and IR + NaHS. The IR was performed by 45 min of ischemia by vessel clamping followed by 24 h reperfusion. The NaHS (100 µmol/kg) treatment was applied 10 min prior to IR. Finally, after 24 h of reperfusion, the measurements were performed. Findings/Results: The serum levels of blood urea nitrogen, creatinine, tissue level of malondialdehyde, and kidney tissue damage score (KTDS) were increased by IR. Urine volume, creatinine, and urea clearances decreased by IR. NaHS administration improved some parameters in males but exacerbated KTDS and serum markers related to renal function. Conclusions and implications: Our data demonstrated that NaHS didn't protect female rats against renal IR injury. In males, it has null effects or just a few protective effects via antioxidant activity.

Unexpected presentation of accessory breast: vulvar accessory breast tissue: a case report.

BACKGROUND: The accessory breast is composed of residual glandular mammary tissue that persists after normal embryonic development. The entity is so rare that it is easily neglected in the diagnosis of disease. CASE PRESENTATION: We report a 24-year-old virgin Persian woman with a left-sided vulvar mass and no pain or discomfort until shortly before her presentation at our department. Ectopic breast tissue in the vulva was diagnosed. We performed wide local resection of the lesion. Pathological investigation of the lesion confirmed the presence of ectopic breast tissue with secretory changes. She had no specific developmental abnormalities and had no relevant family history. She was followed up for 10 months and had recovered fully by this time. CONCLUSION: Accessory breast tissue should be considered as a diagnosis when a mass is seen along the embryonic milk line, especially if the clinical findings reveal changes in the mass accompanied by changes in sex hormones.

Beneficial effects of time and energy restriction diets on the development of experimental acute kidney injury in Rat: Bax/Bcl-2 and histopathological evaluation.

People's lifestyles and, especially, their eating habits affect their health and the functioning of the organs in their bodies, including the kidneys. One's diet influences the cells' responses to stressful conditions such as acute kidney injury (AKI). This study aims to determine the preconditioning effects of four different diets: energy restriction (ER) diet, time restriction (TR) eating, intermittent fasting (IF), and high-fat diet (HF) on histopathological indices of the kidney as well as the molecules involved in apoptosis during AKI. Adult male rats underwent ER, TR, IF, and HF diets for eight weeks. Then, AKI was induced, and renal function indices, histopathological indices, and molecules involved in apoptosis were measured. In animals with AKI, urinary albumin excretion, serum urea, creatinine and, Bax/Bcl-2 ratio increased in the kidney, while renal eGFR decreased. ER and TR diets improved renal parameters and prevented an increase in the Bax/Bcl-2 ratio. The IF diet improved renal parameters but had no effect on the Bax/Bcl-2 ratio. On the other hand, the HF diet worsened renal function and increased the Bax/Bcl-2 ratio. Histopathological examination also showed improved kidney conditions in the ER and TR groups and more damage in the HF group. This study demonstrated that ER and TR diets have renoprotective effects on AKI and possibly cause the resistance of kidney cells to damage by reducing the Bax/Bcl-2 ratio and improving apoptotic conditions.

TERT Promoter Mutations as Simple and Non-Invasive Urinary Biomarkers for the Detection of Urothelial Bladder Cancer in a High-Risk Region.

Bladder cancer (BC) is the 10th most common cancer in the world. While there are FDA-approved urinary assays to detect BC, none have demonstrated sufficient sensitivity and specificity to be integrated into clinical practice. Telomerase Reverse Transcriptase (TERT) gene mutations have been identified as the most common BC mutations that could potentially be used as non-invasive urinary biomarkers to detect BC. This study aims to evaluate the validity of these tests to detect BC in the Kerman province of Iran, where BC is the most common cancer in men. Urine samples of 31 patients with primary (n = 11) or recurrent (n = 20) bladder tumor and 50 controls were prospectively collected. Total urinary DNA was screened for the TERT promoter mutations (uTERTpm) by Droplet Digital PCR (ddPCR) assays. The performance characteristics of uTERTpm and the influence by disease stage and grade were compared to urine cytology results. The uTERTpm was 100% sensitive and 88% specific to detect primary BC, while it was 50% sensitive and 88% specific in detecting recurrent BC. The overall sensitivity and specificity of uTERTpm to detect bladder cancer were 67.7% and 88.0%, respectively, which were consistent across different tumor stages and grades. The most frequent uTERTpm mutations among BC cases were C228T (18/31), C250T (4/31), and C158A (1/31) with mutant allelic frequency (MAF) ranging from 0.2% to 63.3%. Urine cytology demonstrated a similar sensitivity (67.7%), but lower specificity (62.0%) than uTERTpm in detecting BC. Combined uTERTpm and urine cytology increased the sensitivity to 83.8%, but decreased the specificity to 52.0%. Our study demonstrated promising diagnostic accuracy for the uTERTpm as a non-invasive urinary biomarker to detect, in particular, primary BC in this population.

The effect of two types of diet on apoptosis indexes, lipid profile and histopathological outcome in acute kidney injury during exercise.

BACKGROUND: Exercise and some pre-AKI diets have been shown to improve injury, apoptosis, and lipid profile. In this study, the effect of two different diets along with exercise training on acute kidney injury (AKI) was investigated.  MATERIALS AND METHODS: Laboratory rats were randomly divided into four groups of control, standard diet + exercise, exercise + calorie restriction (CR) and exercise + time restriction (TR). Each group was divided into two subgroups of AKI and no AKI. The animals received endurance training and diet regimens before AKI. Fasting blood glucose, serum creatinine, Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl2) and histopathological outcome of renal tissue as well as serum lipid profile of animals were assessed 24 h after AKI.  RESULTS: The percentage of changes in renal Bcl2 and Bax after AKI in the group with previous exercise was lower than the group without previous exercise (p < 0.01). After induction of AKI, serum lipid profile changed in non-exercised rats (p < 0.001). Also, after injury, fasting blood glucose levels increased in non-exercised rats (p < 0.05). After injury, the start of both CR and TR diets during exercise caused less change in Bcl2 and Bax of non-exercised rats compared to exercised rats (p < 0.001). CR diet along with exercise improved lipid profile, and also CR diet along exercise decreased fasting blood glucose levels (p < 0.001). Also, both the CR and TR diets during exercise caused fewer changes in histopathological outcome after AKI. CONCLUSION: Exercise alone decreased changes in apoptotic and histopathological indexes, fasting blood glucose, as well as lipid profile of rats after AKI. Reduction of apoptosis and improvement of histopathological outcome after AKI appeared more when CR and TR diets were commenced during exercise. The reduction of lipid profile changes was more pronounced in the group that received CR diet during exercise.

Effects of caloric and time restriction diets on kidney health in rat model of postmenopausal acute kidney injury: An apoptosis and histopathological study.

Objectives: Lifestyle and eating habits affect the health and function of the body's organs, including the kidneys. The current study was carried out to determine the effects of two types of diet programs, including time restriction (TR) and calorie restriction (CR) on the histopathological changes and apoptotic molecules during acute kidney injury (AKI) in postmenopausal rats. Materials and Methods: In this study the female rats were divided into two groups of ovariectomized (OVX) and ovary-intact (sham), then they were placed on TR and CR diets for 8 weeks; afterward, AKI was induced by injection of glycerol. Functional indices, histopathological changes, Bax, and Bcl2 were measured before and after AKI. Results: After AKI, creatinine, serum urea, urinary albumin excretion, kidney tissue Bax, and Bax/Bcl2 ratio increased, while glomerular filtration rate (GFR) and kidney tissue Bcl2 decreased compared with before AKI. Histopathological indices (inflammation, cellular necrosis, cell vacuolization, tubular dilatation, intratubular cast, and congestion) also confirmed renal injury. TR and CR diets improved renal injury indices and prevented an increase in the Bax/Bcl2 ratio. However, in some indices, the effects of two diets on OVX animals were not observed. In addition, none of the diets could decrease kidney weight/body weight ratio (KW/BW). The histopathological finding also showed improvement of renal status in both groups, especially in the CR diet. Conclusion: The results indicated that TR and CR diets had renoprotective effects against AKI by reducing the Bax/Bcl2 ratio and improving apoptosis. The effects of CR were more than TR.

The evaluation of the relationship between Helicobacter pylori infection and frequency of postoperative complications of laparoscopic sleeve gastrectomy in Shahid Bahonar Hospital in Kerman between 2018 and 2020; a cross-sectional study.

Introduction: Among the bariatric surgery procedures, laparoscopic sleeve gastrectomy (LSG) is one of the most common methods for effective and permanent weight loss among patients with severe obesity. Nonetheless, the LSG can be associated with long-term and short-term complications for the patient. The present study is aimed to investigate the effect of Helicobacter pylori on the complications of LSG, to answer the question of whether eradication of Helicobacter pylori in patients undergoing surgery can be effective in reducing postoperative complications. Methods: In the present analytical-cross sectional study, which has been conducted in Shahid Bahonar Hospital in Kerman during 2018-2020, a total of 100 patients (including 38 males and 62 females) with an average age of 34.8 ± 2.4 years and an average BMI of 41.1 ± 3.1 underwent LSG surgery. After the operation, the gastric mucus specimens were taken from all patients for pathological examination of Helicobacter pylori infection. Results: According to the results, 28 patients (28%) tested positive for Helicobacter pylori infection (HP positive), and 72 patients (72%) tested negative in this regard (HP negative). The results indicated no significant difference between the HP positive and HP negative patients in terms of demographic characteristics (age, gender, BMI). Overall, 11 patients (11%) exhibited postoperative complications of the LSG including 7 cases (7%) of the SSI, 2 cases (2%) of intraoperative bleeding, and 2 cases (2%) of leakage [No mortality was reported]. Out of the 11 patients with postoperative complications, 6 patients were HP positive including 4 cases of SSI, 1 case of bleeding, and 1 case of leakage. Conclusions: As indicated by the obtained results, the HP infection has seemingly no impact on the LSG postoperative complications. Nevertheless, it is necessary to conduct further studies on a larger number of patients with a longer follow-up time focusing on the effect of other parameters, such as BMI and underlying diseases.

Effects of Botulinum Toxin Type A on the Axial Skin Flap Survival.

BACKGROUND: A suitable pharmacological substitute for the well-established surgical delay technique for axial skin flaps regarding increasing viability is elusive. We aimed to evaluate the effects of botulinum toxin type A (BTA) on the axial skin flap survival in a rat model. METHODS: The present controlled experimental study was performed in Kerman University of Medical Science, Kermanshah, Iran during 2016-2017 on three groups of rats. Group 1 (control group) had no preconditioning while Groups 2 and 3 were preconditioned by the intradermal injection of normal saline (0.5 ml) in the cephalic end of the skin flap and the injection of the BTA (1.6 units Neuronex) reconstituted in normal saline, respectively. Two weeks after this intervention in each group, the flap was raised and kept in situ and a biopsy was simultaneously taken for evaluating neoangiogenesis, followed by evaluating flap necrosis after two weeks of following-up by photography. RESULTS: Although BTA induced angiogenesis significantly, it failed to reduce the area of necrosis compared to the other groups. CONCLUSION: BTA was effective in increasing angiogenesis in the axial skin flap although it was unable to reduce necrosis.

The Effect of Cell-Deprived Platelet Lysate Growth Factors (PLGF) on the Perichondrium Preserved Cartilage Graft Viability.

BACKGROUND: Finding a suitable pharmacological substance and a surgical method for improving cartilage graft preparation are necessary. This present study was planned to evaluate the effects of PLGF and graft preparation methods on cartilage graft survival. METHODS: This controlled, experimental study was performed in Kerman University of Medical Science, Kerman, Iran during 2016- 2017 on two groups of rabbits. Group 1 received PLGF (PLGF +) while Group 2 did not receive any PLGF (PLGF -). In each group, three carilage graft preparation methods including Block Cartilage Graft (BCG), Diced Cartilage Graft (DCG), and Crashed Cartilage Graft (CCG) were used. Three months after the intervention, the grafts were re-assessed and weighed. A specimen from each graft was taken for inflammation, fibrosis, necrosis, and viable chondrocyte. RESULTS: The CCG method had the maximum ossification percentage (OS%) and no change occurred by PLGF. The BCG method had the greatest viable chondrocyte number, attenuated by PLGF. The BCG method had the highest amount of fibrosis, without any change by PLGF. Additionally, the inflammation percentage and necrosis in the PLGF + group were greater than the PLGF - group. CONCLUSION: The most important effecting factor on the properties of cartilage graft is the method of graft preparation and PLGF only attenuates the methods properties without changing them.

Possible involvement of female sex steroid hormones in intracellular signal transduction mediated by cytokines following traumatic brain injury.

INTRODUCTION: The aim of this study was to determine the anti-inflammatory effect of female sex hormones on the level of intracellular molecules of cytokine signaling pathway after diffuse traumatic brain injury (TBI) in ovariectomized rats. METHODS: Female rats were divided into 10 groups: control, sham, TBI, Vehicle (oil), Vehicle E1 (33.3 µg/kg), E2 (1 mg / kg), P1 (1.7 mg/kg), P2 (8 mg / kg), E2 + P1. All drugs were injected 0.5 h after TBI. Brain edema and the brain levels of P-STAT-3, NFκB-P52, NFκB-P65, P-IκB, and SOCS-3 by immunohistochemistry measured at 24 h after TBI. RESULTS: Increased brain edema after TBI was inhibited by different doses of estrogen, progesterone (P < 0.001), and E2 + P1 (P < 0.05). The brain levels of P-STAT-3, NFκB-P52, NFκB-P65, and p-IκBα that increased after TBI was decreased only by E2 (P < 0.05). E2 and E2 + P1 have increased the SOCS-3 level after TBI (P < 0.05). Also, there was a difference between the E2 with E1 and two progesterone doses (P < 0.05). So that in all cases, the effects of E2 were more significant than the other groups. The target cells for these effects of E2 were microglia and astrocytes. CONCLUSION: The results indicate that one of the probable mechanism(s) of estrogen anti-inflammatory effect after TBI is either reduction of p-STAT-3, NFκB-P52, p-NFκB-P65, and p-IκBα or increase in SOCS-3 molecules involved in the signaling pathway of inflammatory cytokines.

Preparation and evaluation of crocin loaded in nanoniosomes and their effects on ischemia-reperfusion injuries in rat kidney.

As a powerful antioxidant compound, crocin can partially protect against renal ischemia/reperfusion (I/R) injuries. The encapsulation of components in niosomes (non-ionic surfactant-based vesicle) as nano-sized carrier systems has been proposed as they improve the solubility, stability, and bioavailability of drugs. Herein, the encapsulation of crocin in nano-niosomes and the effects of crocin-loaded nano-niosomes on renal ischemia/reperfusion-induced damages were evaluated. Nano-niosomes containing crocin were formulated by a modified heating method and were characterized for their physicochemical characteristics. Ischemia was induced by clamping the renal artery for 30 min followed by 1 or 24 h of reperfusion. Rats received an intra-arterial injection of nano-niosome-loaded crocin at the outset of reperfusion. Blood samples were taken after reperfusion to measure urea, creatinine (Cr), malondialdehyde (MDA), and superoxide dismutase (SOD) activity. The right kidney was removed for histological examination. The results showed that crocin-contain nano-niosomes have appropriate size and morphology, acceptable encapsulation efficiency, and a proper release pattern of crocin. I/R enhanced creatinine (Cr), urea, and malondialdehyde (MDA) serum levels and reduced SOD activity and histological damages in the renal tissue.

Epidemiological Study of Various HPV Strains in Cervical Fluid Samples in South-Eastern Iran, 2018-2020.

BACKGROUND: Uterine cervical malignancy is one of the commonly detected malignancies related to the human papillomavirus (HPV) and is increasing incidentally in developing countries. Therefore, the use of an efficient diagnostic method is required as an effectual step for cervical cancer prevention and treatment. The purpose of the study was to diagnose various types of HPV in the cervical cytology specimens in the South-East of Iran. METHODS: This cross-sectional study was performed on 1079 cervical fluid cytology specimens referred for two years, between 2018-2020. Polymerase chain reaction (PCR) and hybridization (INNO-LiPA HPV Genotyping EXTRA II assay) were used to determine HPV DNA and their genotypes, respectively. RESULTS: HPV was positive in 37.7% (407 of 1079) patients with a mean age of 34.62 ± 8.82. Among positive cases, 252 (62%) had only one HPV genotype and 155 (38.05%) had multiplex HPV genotypes, which included 94 (60.7%), 38 (24.6%), 18 (11.6%) and 5 (3.2%) cases with two, three, four and five or more genotypes, respectively. The samples with multiple strains revealed 31 HPV genotypes with the four most prevalent being HPV6 (14.7%), HPV16 (10.9%), HPV53 (9.6%) and HPV51 (5.9%). CONCLUSION: HPV infection is the main health challenge for women that requires improved health service programs and appropriate epidemic vaccination.

Evaluation of the protective effect of curcumin on encephalopathy caused by intrahepatic and extrahepatic damage in male rats.

OBJECTIVES: Along with increased intracranial pressure (ICP) and brain damage, brain edema is the most common cause of death in patients with hepatic encephalopathy. Curcumin can pass the blood-brain barrier and possesses anti-inflammatory and anti-oxidant properties. This study focuses on the curcumin protective effect on intrahepatic and extrahepatic damage in the brain. MATERIALS AND METHODS: One hundred and forty-four male Albino N-Mary rats were randomly divided into 2 main groups: intrahepatic injury group and extrahepatic cholestasis group. In intra-hepatic injury group intrahepatic damage was induced by intraperitoneal (IP) injection of acetaminophen (500 mg/kg) [19] and included four subgroups: 1. Sham, 2. Acetaminophen (APAP), 3. Normal saline (Veh) which was used as curcumin solvent, and 4. Curcumin (CMN). In extrahepatic cholestasis group intrahepatic damage was caused by common bile duct litigation (BDL) and included four subgroups: 1. Sham, 2. BDL, 3. Vehicle (Veh), and 4. Curcumin (CMN). In both groups, 72 hr after induction of cholestasis, brain water content, blood-brain barrier permeability, serum ammonia, and histopathological indicators were examined and ICP was measured every 24 hr for three days. RESULTS: The results showed that curcumin reduced brain edema, ICP, serum ammonia, and blood-brain barrier permeability after extrahepatic and intrahepatic damage. The maximum effect of curcumin on ICP was observed 72 hr after the injection. CONCLUSION: According to our findings, it seems that curcumin is an effective therapeutic intervention for treating encephalopathy caused by extrahepatic and intrahepatic damage.

An Unusual Presentation of Giant Fibroepithelial Polyp of the Vagina.

Fibroepithelial polyps of the vagina (FEPV) are rare entities which normally manifest as one or more painless polyps sometimes with symptoms such as bleeding, vaginal discharge, and discomfort regarding the size of the mass. Despite their benign nature, they can be confused with other vaginal tumors due to their abnormal histology. In this report, we present a case of a 44-year-old woman with a giant pedunculated and symptomatic polyp of the vagina with anterior vaginal wall prolapse. The treatment method included a simple local excision of the polyp and anterior vaginal compartment repair. Histopathological examination revealed a polypoid lesion covered by squamous epithelium containing a central fibrovascular core without atypia. The patient experienced an uneventful postoperative recovery, with no complication, which implies that surgery is the most effective modality for managing such tumors.

A Giant Solid-Cystic Mesenteric Fibromatosis with Unusual Synchronous Skin Fibromatosis.

Mesenteric fibromatosis (MF) is a rare, locally aggressive tumor without distant metastasis, which has a high recurrence rate. Based on its location, it is classified as intra-abdominal, from abdominal wall, and extra-abdominal. The incidence of cystic-solid, retroperitoneal tumors is very low in comparison to other MF forms. Intra-abdominal MFs are asymptomatic in early stages, but their symptoms appear late in the tumor course. There is no specific imaging finding since radiological diagnosis is mostly impossible. Thus, diagnosis is made histopathologically. Nowadays, there is no consensus about its treatment although surgical resection is widely used. In the present study, a very rare case of cystic-solid retroperitoneal MF associated with separate synchronous skin tumors is reported.

Expression of P63, P16 and CK17 in Atypical Squamous Metaplasia and Cervical Intraepithelial Neoplasia.

BACKGROUND & OBJECTIVE: Cervical intraepithelial neoplasia (CIN) is a dysmaturation process in squamous cells in epithelial layer, which highly increases the risk of developing cervical cancer. The aim of this study was to compare the expression of three biomarkers, p16, p63, and CK17 in patients with CIN and in those with atypical squamous metaplasia (ASM). METHODS: In this study, 100 patients underwent a colposcopy-guided cervix biopsy. Immunostaining for the biomarkers was undertaken on tissue samples presented with ASM (n=50) and CIN (n=50). RESULTS: A significant increase in immunostaining for CK7, P63, and P16 in patients with CIN was found compared to ASM subjects. CONCLUSION: Expression of CK17, P63, and P16 in CIN varied from those in ASM. Those biomarkers could be reliable factors to distinguish ASM from CIN; however, all the biomarkers could differentiate CIN from its mimics due to their high degree of sensitivity and specificity.

Perillyl alcohol suppresses monocrotaline-induced pulmonary arterial hypertension in rats via anti-remodeling, anti-oxidant, and anti-inflammatory effects.

Background: Pulmonary arterial hypertension (PAH) is a disastrous disease that current treatments cannot prevent its progression. The present study investigated the effects of perillyl alcohol (PA), a natural monoterpene, on the experimental PAH in male Wistar rats. Methods: Rats divided into eight groups of control, Monocrotaline (MCT), MCT+vehicle, and MCT+PA with doses of 20, 30, 40, 50, and 60 mg/kg. PAH was induced by a single injection of monocrotaline (60 mg/kg) on day 0. The animals in the groups of MCT+vehicle and MCT+PA received the vehicle or PA from day 22 to 42 once a day. On day 43, under general anesthesia, right ventricular systolic pressure (RVSP), as an index of pulmonary artery systolic pressure, and the ratio of the right ventricle to the left ventricle plus septum weight, as the right ventricular hypertrophy index (RVHI), were measured. Also, some histological and biochemical indices were assessed in the lung tissue. Results: MCT significantly (p < .001) enhanced the RVSP and RVHI compared to the control group (89.4 ± 8.2 vs 23 ± 3.3 mmHg & 0.63 ± 0.08 vs 0.26 ± 0.04 respectively). It also increased oxidative stress and inflammatory cytokines and reduced Bax/Bcl2 ratio. Treatment with PA significantly recovered RVSP and hypertrophy index and suppressed vascular cell proliferation, oxidant production, and inflammatory processes. Conclusion: PA exerted noticeable protective and curative effects against MCT-induced PAH and pulmonary vascular remodeling through inhibiting cellular proliferation, oxidative stress, and inflammation. Therefore, PA can be considered as a new therapeutic goal for the treatment of PAH.

Swimming Exercise Training Attenuates the Lung Inflammatory Response and Injury Induced by Exposing to Waterpipe Tobacco Smoke.

BACKGROUND: The use of waterpipe tobacco smoking (WTS) is on the rise throughout the world, especially among young people and even athletes. There is a belief among consumers that exercise prevents the harmful effects of hookah smoke on the body. We examined this belief by evaluation of lung injury following to concurrent WTS and swimming endurance training in male Wistar rats. METHODS: Animals were randomly divided to sedentary control (CTL) group, exercise training group (Ex group), sedentary WTS (S) group, and exercise plus WTS (S + Ex) group. FINDINGS: 8 weeks of WTS was associated with significant increase in serum level of cotinine, lung damage, reduction in alveolar number AN/SA (mm2) and increase in malondialdehyde (MDA) level of lung tissue. Combination of exercise with WTS significantly decreased these negative effects; however, it could not fully protect the lung from smoking damage. Waterpipe smoking (WPS) also significantly increased the pro-inflammatory cytokines of lung tissue such as tumor necrosis factor alpha (TNF-α) (P < 0.001), interleukin 1 beta (IL-1ß) (P < 0.010), and IL-6 (P < 0.050) in comparison with CTL group. Exercise training to some degree reduced the levels of pro-inflammatory cytokines and increased the level of IL-10 as an anti-inflammatory IL and glutathione peroxidase (GPX) activity in animals exposed to WTS. CONCLUSION: It is suggested that combination of mild to moderate exercise with WTS may attenuate the hookah smoking-induced lung damage. This effect partly is mediated through balancing of pro/anti-inflammatory and redox systems.