Improved therapy for clear cell renal cell carcinoma: beta-hydroxybutyrate and quercetin target hypoxia-induced angiogenesis and multidrug resistance.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a form of kidney cancer characterized by dysregulated angiogenesis and multidrug resistance. Hypoxia-induced tumor progression plays a crucial role in ccRCC pathogenesis. Beta-hydroxybutyrate (BHB) and quercetin (QCT) have shown potential in targeting angiogenesis and drug resistance in various cancer types. This study investigates the combined effects of BHB and QCT in hypoxia-induced Caki-1 cells. METHODS: Caki-1 cells were subjected to normoxic and hypoxic conditions and treated with BHB, QCT, or a combination of both. Cell-viability was assessed using the MTT assay, and mRNA expression levels of key angiogenesis-related genes (HIF-1α/2α, VEGF, Ang-1, Ang-2, and MDR4) were quantified through real-time PCR during 24 and 48 h. RESULTS: BHB and QCT treatments, either alone or in combination, significantly reduced cell-viability in Caki-1 cells (p < 0.05). Moreover, the combined therapy demonstrated a potential effect in downregulating the expression of angiogenesis-related genes and MDR4 in hypoxia-induced cells, with a marked reduction in HIF-1α/2α, VEGF, Ang-1, and MDR4 expression (p < 0.05). The expression of Ang-2 increases significantly in presence of BHB combined QCT treatment. CONCLUSION: This study highlights the promising potential of a combination therapy involving BHB and QCT in mitigating angiogenesis and MDR4 expression in hypoxia-induced ccRCC cells. These findings support further investigation into the underlying mechanisms and warrant clinical studies to evaluate the therapeutic value of this combined treatment for ccRCC patients. This research provides new insights into addressing the challenges posed by angiogenesis and drug resistance in ccRCC.

Factors disrupting the continuity of care for patients with chronic disease during the pandemics: A systematic review.

Background and Aims: Continuous routine care is necessary to prevent long-term complications of chronic diseases and improve patients' health conditions. This review study was conducted to determine the factors disrupting continuity of care for patients with chronic diseases during the pandemic. Methods: All original articles published on factors disrupting continuity of care for patients with chronic disease during a pandemic between December 2019 and June 28, 2023, in PubMed, Web of Science, Scopus, and ProQuest databases were searched. Selection of articles, data extraction, and qualitative evaluation of articles (through STROBE and COREQ checklist) were done by two researchers separately. Data graphing form was used to extract the data of each study and then the data were classified by thematic analysis method. Results: Out of 1708 articles reviewed from the databases, 22 were included. The factors disrupting the continuity of care for patients with chronic diseases during the epidemics were classified into two main categories: patient-side factors and health system-side factors. Patient-side factors including psychological, individual and social, disease-related, and health system-side factors including provider access, health system institutional, and infrastructural and financial problems were among the subcategories disrupting the continuity of care for patients with chronic diseases during the pandemic. Based on the studies, psychological factors and access to the provider were among the most frequent factors affecting the continuity of care for patients with chronic diseases in the pandemic. Conclusion: Considering the factors disrupting the continuity of care and applying appropriate interventions based on them, can guarantee the continuity of providing services to chronic patients in health crises.

Targeting apoptosis and unfolded protein response: the impact of ß-hydroxybutyrate in clear cell renal cell carcinoma under glucose-deprived conditions.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) plays a significant role in the mortality associated with kidney cancer. Targeting biological processes that inhibit cancer growth opens up new treatment possibilities. The unfolded protein response (UPR) and apoptosis have crucial roles in RCC progression. This study investigates the impact of ß-hydroxybutyrate (BHB) on ccRCC cells under glucose deprivation resembling as a ketogenic diet. METHOD: Caki-1 ccRCC cells were exposed to decreasing glucose concentrations alone or in combination with 10 or 25 mM BHB during 48 and 72 h. Cell viability was determined using MTT assay. The mRNA expression level of apoptosis-and UPR-related markers (Bcl-2, Bax, caspase 3, XBP1s, BIP, CHOP, ATF4, and ATF6) were assayed by qRT-PCR. RESULTS: Cell viability experiments demonstrated that combining different doses of BHB with decreasing glucose levels initially improved cell viability after 48 h. Nevertheless, this trend reversed after 72 h, with higher impacts disclosed at 25 mM BHB. Apoptosis was induced in BHB-treated cells as caspase-3 and Bax were increased and Bcl-2 was downregulated. BHB supplementation reduced UPR-related gene expression (XBP1s, BIP, CHOP, ATF4, and ATF6), revealing a possible mechanism by which BHB affects cell survival. CONCLUSION: This research emphasizes the dual effect of BHB, initially suppressing cell- survival under glucose deprivation but eventually triggering apoptosis and suppressing UPR signaling. These data highlight the intricate connection between metabolic reprogramming and cellular stress response in ccRCC. Further research is recommended to explore the potential of BHB as a therapeutic strategy for managing ccRCC.

Proton-pump inhibitor-induced bone loss is preventable by concomitant use of a long-acting somatostatin analogue.

Objectives: Long-term consumption of pump inhibitors causes osteoporosis. Some possible mechanisms are gastrin over-secretion and hypochlorhydria. Octreotide is a somatostatin analog that inhibits the secretion of many hormones such as gastrin. This study aimed to assess the effects of pantoprazole on the bone when used with octreotide in an animal model. Materials and Methods: Forty-eight male Wistar rats were randomly assigned into 4 groups: A) pantoprazole 3 mg/Kg/day orally; B) Sandostatin LAR 1 mg/month intramuscular injection; C) Pantoprazole and Sandostatin LAR; and D) Control group. After 90 days of the experiment, bone densitometry was done and serum and urine samples were collected for analysis. Results: The results indicated a significant decrease in the global, spine, femur, and tibia bone mineral density (BMD) and bone mineral content (BMC) in the pantoprazole group compared to the control group (P<0.05). There was a significant increase in the levels of PTH, gastrin, and alkaline phosphatase (ALP) in the pantoprazole group compared to the control group (P<0.05). There was no significant difference in the serum levels of gastrin, PTH, ALP, and also BMD in the rats that received sandostatin+ pantoprazole or sandostatin alone, compared to the control group. Conclusion: This study showed that the pantoprazole-induced bone loss, through elevation of serum gastrin and PTH, was preventable by concomitant use of a long-acting somatostatin analog.

The Effects of Ginger (Zingiber Officinale Roscoe) on Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus: A Randomized Double-Blinded Placebo-Controlled Clinical Trial.

Nonalcoholic fatty liver disease (NAFLD) is a prominent etiological factor for liver cirrhosis worldwide. It is frequently associated with obesity, diabetes, dyslipidemia, and hypertension. The objective of this study is to assess the efficacy and safety of ginger (Zingiber officinale Roscoe) supplementation in patients with type 2 diabetes mellitus (T2DM) who have NAFLD. In a two-arm, double-blind, placebo-controlled clinical trial, seventy-six patients diagnosed with both T2DM and NAFLD were randomly assigned to receive either ginger powder capsules (1000 mg, twice daily) or placebo capsules (administered in the same manner) for a period of three months. Anthropometric measurements, blood pressure readings, biochemical profiles, and imaging parameters were assessed before and after the intervention. Safety measures were also evaluated. In both the ginger and placebo groups, there was a significant reduction in mean body mass index (BMI), waist and hip circumferences, as well as liver transaminase levels. Moreover, significant improvements in mean systolic and diastolic blood pressures were observed in the ginger group (p = 0.02 and < 0.0001, respectively). Within the ginger group, there was a decrease in serum insulin levels and insulin resistance (HOMA-IR) (p = 0.002 and 0.004, respectively). Furthermore, the ginger group exhibited an improvement in serum HDL-cholesterol level (p = 0.01). However, there were no significant changes in the assessed inflammatory markers or the indices obtained from fibroscan imaging, including steatosis percent and controlled attenuation parameter. This study demonstrates that ginger supplementation can significantly improve mean systolic and diastolic blood pressures. However, it does not have a significant impact on inflammatory markers or fibroscan imaging indices. Nonetheless, the three-month use of ginger improves serum insulin level, insulin resistance (HOMA-IR), and HDL-cholesterol level compared to baseline values. Further investigations with longer durations and larger sample sizes are recommended.

Pantoprazole-Induced Bone Loss through Gastrin Secretion: A Stereological Study.

Background: Recent researches have failed to uncover a clear explanation for proton pump inhibitors' bone-loss effects. In light of pantoprazole's effects on gastrin secretion, the goal of this study was to see if it caused bone loss through gastrin secretion. Methods: Forty male rats were divided into control, octreotide (Oct), pantoprazole (Pan), and pantoprazole plus octreotide (Pan+Oct) groups. Serum calcium, phosphorous, alkaline phosphatase, parathyroid hormone, and gastrin were measured before and three months after the treatment, and bone densitometry was examined. The rats' femoral bones were examined stereologically at the end of the investigation. Results: The Pan group had considerably greater levels of serum alkaline phosphatase, parathyroid hormone (PTH), and gastrin, but this was prevented in the presence of Oct, a gastrin secretion inhibitor. All parameters of femoral bone densitometry in the Pan group were significantly lower than the control after treatment which was considerably inhibited in the presence of Oct. Furthermore, when compared to the control and Oct groups, the rats in the Pan group had a lower trabecular volume, femur bone weight, and volume, as well lower number of osteocytes. The amount of osteoclasts, on the other hand, was much higher in the Pan group than in the other groups. Conclusion: Overall findings revealed that pantoprazole caused bone loss, which could be prevented by adding octreotide. Because these detrimental effects were not detected in rats given both Oct and Pan, it was suggested that the effect of Pan on bone was produced by a hypergastrinemic condition.

Association between Nontraditional Risk Factors and Calculated 10-Year Risk of Atherosclerotic Cardiovascular Disease in a Large General Population: Based on the Pars Cohort Study.

Background: While the traditional risk factors of atherosclerotic cardiovascular disease (ASCVD) have been well-established, the evolving role of nontraditional risk factors is not apparent. This study aimed to evaluate the association between nontraditional risk factors and the calculated 10-year ASCVD risk in a general population. Methods: This cross-sectional study was conducted using the Pars Cohort Study data. All inhabitants of the Valashahr district in southern Iran, aged 40-75 years, were invited (2012-2014). Patients with a history of cardiovascular disease (CVD) were excluded. The demographic and lifestyle data were collected using a validated questionnaire. Multinomial logistic regression analysis was used to evaluate the association between the calculated 10-year ASCVD risk and the nontraditional risk factors of CVD, including marital status, ethnicity, educational level, tobacco and opiate consumption, physical inactivity, and psychiatric disorders. Results: Of 9264 participants (mean age =52.2±9.0 y; 45.8% male), 7152 patients met the inclusion criteria. In total, 20.2%, 7.6%, 36.3%, 56.4%, and 46.2% of the population were cigarette smokers, opiate consumers, tobacco consumers, ethnically Fars, and illiterate, respectively. The prevalence rates of low, borderline, and intermediate-to-high 10-year ASCVD risks were 74.3%, 9.8%, and 16.2%, respectively. In multinomial regression, anxiety (adjusted odds ratio [aOR], 0.58; P<0.001) was significantly associated with a lower ASCVD risk, whereas opiate consumption (aOR, 2.94; P<0.001) and illiteracy (aOR, 2.48; P<0.001) were significantly associated with a higher ASCVD risk. Conclusion: Nontraditional risk factors are associated with the 10-year ASCVD risk and, thus, might be considered besides traditional ones for ASCVD in preventive medicine and health policies.

The effects of soymilk plus probiotics supplementation on cardiovascular risk factors in patients with type 2 diabetes mellitus: a randomized clinical trial.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular diseases. This study aimed to assess the effects of soymilk plus probiotics co-administration on cardiovascular risk factors in T2DM patients. METHODS: One hundred patients with T2DM (aged 40-75 years old) were randomly assigned into 4 groups (soymilk + probiotics supplement, soymilk + placebo, conventional milk + placebo, and probiotics supplement) for 6 weeks. Standard protocols were followed for the collection of fasting blood samples, dietary intakes, and anthropometric measurements. RESULTS: It was shown that soymilk + probiotics consumption significantly decreased diastolic blood pressure (DBP) (p = 0.001), triglycerides (TG) (P < 0.001), total cholesterol (TC) (p < 0.01), and insulin (P < 0.003) levels and significantly increased high-density lipoprotein cholesterol (HDL-C) (P = 0.002) levels. Soymilk + placebo administration significantly decreased DBP (p = 0.01), insulin (p = 0.006), and TG (p = 0.001) levels and significantly increased HDL-C (p = 0.03) levels. A significant decrease in insulin (p = 0.003) and systolic blood pressure (SBP) (p = 0.01) levels and an increase in HDL-C (p = 0.04) levels were observed after supplementation with probiotics. Findings from between-group comparisons showed a significant decrease in SBP levels in the probiotics supplement group compared to conventional milk group (p < 0.05). CONCLUSION: Soymilk and probiotics consumption might improve some cardiovascular risk factors in patients with T2DM. However, possible synergic effects while consumption of soymilk plus probiotics supplement didn't show in this study which warranted further research.

Serum androgens and prolactin levels in patients with keratoconus.

CLINICAL RELEVANCE: There is growing evidence for the involvement of sex hormones in the pathogenesis of keratoconus. BACKGROUND: This study aimed to evaluate serum androgen and prolactin levels in patients suffering from keratoconus. METHODS: One hundred and two subjects were enrolled in the keratoconus (76 patients) and control (26 subjects) groups in a cross-sectional survey. Topographic evaluation of the cornea was undertaken for all enrolled participants. Serum testosterone, dehydroepiandrosterone sulphate (DHEAS), prolactin (PRL), luteinising hormone (LH), and follicle-stimulating hormone (FSH) were measured in all subjects. RESULTS: There was no significant difference in demographic characteristics between the study groups. Significantly higher mean serum levels of DHEAS (3.71 ± 2.23 vs. 2.53 ± 1.77 µg/mL; P = 0.009) and T (6.18 ± 3.80 vs. 1.57 ± 1.76 ng/mL; P < 0.001) were observed in men with keratoconus compared to controls. In females, there were also higher mean levels of DHEAS (2.40 ± 1.57 vs. 2.18 ± 0.72 µg/mL; P = 0.355) and T (0.78 ± 0.96 vs. 0.32 ± 0.13 ng/mL; P < 0.001) in patients with keratoconus but only T level reached the statistically significant level of difference. Also, the mean serum PRL level was significantly higher in women with keratoconus compared to control (13.33 ± 17.85 vs. 4.63 ± 3.10 ng/mL; P < 0.001). There was no significant difference between serum FSH and LH levels between study groups. CONCLUSION: In patients with keratoconus, serum PRL in females and serum androgen levels in both genders are elevated.

New concepts in regulation and function of the FGF23.

In comparison to the regulation of calcium homeostasis, which has been widely studied over the last several decades, phosphate homeostasis is little understood. The parathyroid hormone (PTH)/vitamin D axis has traditionally been used as a conceptual framework for understanding mineral metabolism. Recently, the fundamental regulator of phosphate homeostasis, fibroblast growth factor 23 (FGF23), which is produced by osteocytes and is involved in the hormonal bone-parathyroid-kidney axis, has attracted more attention. The secretion of FGF23 is controlled by diet, serum phosphate levels, PTH, and 1,25(OH)2 vitamin D. FGF-23, the FGF receptors and the obligate co-receptor α-Klotho work in concert to affect FGF-23 actions on targeted organs. Despite all efforts to investigate pleotropic effects of FGF23 in various endocrine organs, many aspects of the regulation and functions of FGF23 and the exact crosstalk among FGF23, serum phosphate, calcium, PTH, and vitamin D in the regulation of mineral homeostasis remain unclear; much efforts need to be established before it can be moved toward therapeutic applications. In this regard, we provide a brief overview of the novel findings in the regulation and function of FGF23 and refer to related questions and hypotheses not answered yet, which can be a window for future projects. We also focus on the current knowledge about the role of FGF23 obtained from our researches in recent years.

Proximal muscle weakness as the sole manifestation of Cushing's disease, misdiagnosed as dermatomyositis: a case report.

BACKGROUND: Cushing's syndrome consists of signs and symptoms related to prolonged exposure to high levels of glucocorticoid, and should be considered in individuals with the discriminatory signs and symptoms. Proximal myopathy is an important discriminatory sign. CASE PRESENTATION: We report the case of a 36-year-old Iranian man who presented with proximal muscle weakness. He visited a rheumatologist in an outpatient clinic, and according to proximal muscle weakness and heliotrope rash (based on the rheumatologist's notes) with the impression of dermatomyositis, prednisolone and azathioprine were prescribed for him that did not improve his clinical status and he was gradually wheelchair dependent. He was admitted to the hospital for evaluation of paraneoplastic syndromes. Standard laboratory tests and imaging were unremarkable, other than a brain magnetic resonance imaging that demonstrated a 30 × 12 mm homogeneously enhancing mass in the sellar region with extension to the suprasellar area. He had serum cortisol of 295 ng/mL, and adrenocorticotropic hormone of 222 pg/mL (on 5 mg prednisolone twice daily), with a diagnosis of Cushing's disease. He underwent two sessions of trans-sphenoidal surgery 4 months apart. After the first surgery, the proximal muscle weakness improved dramatically and he was walking with the aid of a walker, and after the second surgery he is walking without any aids. CONCLUSION: This case report emphasizes the high diagnostic importance of proximal muscle weakness as the sole presenting manifestation of Cushing's syndrome/disease.

Carbulin: A Comprehensive Mobile Application for Advanced Carbohydrate Counting and Diet- and Insulin-Regimen Planning for Type 1 Diabetic Patients.

Nowadays, the introduction of the so-called 'diabetes technology', either hardware/device or software, to different aspects of day-to-day living in patients with diabetes aims to improve blood glucose control and various lifestyle features. The coordination of vast context of diabetes education/training, particularly in the area of medical nutrition therapy, is considered as a great concern. On the other hand, Iranian food culture consists of a set of traditional dietary patterns and food consumption habit. The study was aimed to develop "the Comprehensive Mobile Application of Advanced Carbohydrate Counting and Diet- and Insulin-Regimen Planning" to help type 1 diabetic patients, improving their health status. The programming language of Kotlin, JavaScript, Node JS, and HTML5 was used for the mobile app development. The app was developed with the following abilities: 1) educating users on different aspects of disease control including, updated general treatment guidelines on physical activity, medical nutrition and insulin therapy, stress management, and the patient's specific goals and dietary needs, 2) performing advanced carbohydrate counting using both picture-represented and kitchen-scale of carbohydrate foods as well as traditional Iranian foods, 3) recommending the patient's specific insulin dose, either short- or rapid-acting, based on the carbohydrate content of the selected meal or the selected amount of Iranian foods, 4) recommending the personalized insulin dose needed for decreasing the high blood glucose levels, and 5) performing 3 and 4 simultaneously. Developing Carbulin was an effort to increase type 1 diabetes self-management using the traditional Iranian dietary pattern and menu.

Efficacy of Ginger Supplementation in Relieving Persistent Hypothyroid Symptoms in Patients with Controlled Primary Hypothyroidism: A Pilot Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Primary hypothyroidism is a common disease. Some patients have persistent symptoms despite normal serum thyroid-stimulating hormone (TSH) levels. Ginger is reported to be beneficial in relieving similar symptoms. Our aim was to evaluate the efficacy of ginger supplementation in relieving persistent symptoms in these patients. In this randomized, double-blind, placebo-controlled clinical trial, 60 hypothyroid patients aged 20-60 years with normal serum TSH concentrations were randomly allocated to two equal parallel study groups of ginger (500 mg twice a day) or placebo for 30 days. Hypothyroid symptoms were evaluated as the primary outcome using the Thyroid Symptom Rating Questionnaire (ThySRQ) before and after the intervention. Anthropometric measures and laboratory indices including TSH, triglyceride (TG), total cholesterol (TChol), and fasting blood sugar (FBS) were considered as secondary outcomes. A significant lower mean total ThySRQ score (8.63 ± 5.47 vs. 15.76 ± 6.09, P < 0.001) was observed in the ginger group compared to the control group. Ginger led to significant improvements in the mean scores of the weight gain, cold intolerance, constipation, dry skin, appetite, memory loss, concentration disturbance, and feeling giddy or dizzy domains (P < 0.001). However, no significant improvements were observed in hair loss, nail fragility, hearing, hoarseness, speech, and depression or feeling down (P > 0.05). Ginger supplementation also led to a significant decrease in body weight, body mass index, waist circumference, serum TSH, FBS, TG, and TChol levels compared to the placebo. In summary according to preliminary results of this study, ginger supplementation can help relieve persistent hypothyroid symptoms. Also, it may have beneficial effects in terms of weight reduction and regulation of the FBS and lipid profile in hypothyroid patients.

Cosmetic use and serum level of lead (not cadmium) affect bone mineral density among young Iranian women.

Bone mineral density is a crucially important index for skeletal health. A low amount of bone density (osteoporosis) is a common health problem among men and especially women. Among different parts of the body, women's face is the area on which many types of (facial) cosmetics are routinely applied. The aims of this study were to measure the association of cosmetic use with BMD of the lumbar spine and femoral neck among young female students. This is a cross-sectional study on 65 female students in the 2017 academic year. The study participants were students at Shiraz University of Medical Sciences who were selected randomly using phone directory sampling method. Based on the results of multiple linear regression, adjusted for several important covariates, cosmetic use is inversely associated with the BMD z-scores. Lead was significantly associated with trochanteric z-score (B = -0.002 to 95% CI = -0.004 to -0.0003, p = 0.02) and total lumbar z-score (B = -0.002 to 95% CI = -0.004 -0.0005, p = 0.01). In the present study, duration of using cosmetics was significantly associated with BMD of key skeletal regions. The big market of cosmetics in many countries especially those in the Middle East is highly a vastly neglected health issue. Many more observational prospective or interventional studies are required to understand the benefits and hazards caused by cosmetics in women.

Determinants of serum adiponectin levels: a cross-sectional study.

OBJECTIVES: To review non-surgical prevention strategies in women with hereditary breast and ovarian cancer syndromes. CONTENT: Women with a gBRCA1 or 2 mutations face a high cumulative breast and ovarian cancer risk. While bilateral mastectomy (PBM) and bilateral salpingo-oophrectomy (PBSO) profoundly reduce the respective cancer risks, they are also associated with considerable side effects. There is therefore an urgent need for alternative and non-surgical risk reduction options. Tamoxifen and aromatase inhibitors have both been evaluated in secondary prevention, but their benefit in primary prevention is currently unknown in BRCA mutation carriers. In addition, their use is compromised by their side effect profile which makes them less appealing for a use in chemoprevention. SUMMARY AND OUTLOOK: Denosumab is a well-tolerated osteoprotective drug, which has been demonstrated to have a potential preventive effect particularly in BRCA1-deficient models in vitro. The prospectively randomized double-blind BRCA-P trial is currently investigating the preventative effect of denosumab in healthy BRCA1 germ line mutation carriers.

Educating Health Science Students About Peace through Health Topic; A Panel Discussion.

This report describes an experience of the first international health for peace conference held in November 2018 in Shiraz University of Medical Sciences. This paper discusses the panel on peace education in medical and paramedical schools and the way for the future.

Efficacy of inhaled Lavandula angustifolia Mill. Essential oil on sleep quality, quality of life and metabolic control in patients with diabetes mellitus type II and insomnia.

ETHNOPHARMACOLOGIC RELEVANCE: Lavandula angustifolia Mill (lavender) odor was traditionally used as sleep enhancer. Previous studies have shown interaction between insomnia, quality of life and control of diabetes mellitus (DM). Insomnia is suggested to increase the risk of depression and decrease the quality of life in diabetic patients. The aim of this study was to evaluate the efficacy of inhaled Lavandula angustifolia Mill. as a complementary therapy for insomnia in diabetic patients. METHODS: In a randomized crossover placebo-controlled clinical trial, 52 patients with type II diabetes mellitus (DM) and insomnia, defined as Pittsburgh Insomnia Rating Scale-20(PIRS-20)>5,were treated with inhaled lavender or placebo for two periods of 4 weeks duration with one week interval as washing period. Sleep quality, quality of life and mood status were assessed by PIRS-20, WHO Quality of Life-BREF(WHOQOL-BREF) Questionnaire and Beck Depression Inventory (BDI) scale respectively, at baseline and end of each period of study. Fasting blood glucose (FBS), calorie intake and physical activity were measured before and after the interventions. RESULTS: At the end of study, data of 37 patients (all received both lavender and placebo in cross-over design) were analyzed. Based on crossover analysis the first treatment was not effective on the second treatment. Inhaled lavender resulted in a significant better outcome compared to placebo according to mean PIRS-20, WHOQOL-BREF and Beck Depression Inventory scores in both crossover arms. Likewise there was a significant better outcome in PIRS-20 domains for quality and quantity of sleep after Inhaled lavender compared to placebo. No significant improvement was observed in fasting glucose in lavender compared to placebo administration period. CONCLUSION: Inhaled lavender can improve sleep quality and quantity, quality of life and mood in diabetic patients suffering from insomnia with no significant effect on metabolic status.

Effects of Citrullus colocynthis L. in a rat model of diabetic neuropathy.

OBJECTIVE: This study investigated the biochemical, histopathological and physiological effects of Citrullus colocynthis on peripheral neuropathy in rats with streptozotocin (STZ)-induced diabetes. METHODS: Seventy adult male Sprague-Dawley rats were included in the present study. Diabetes was induced in 60 rats, with a single intraperitoneal injection of STZ (65 mg/kg). After 4 weeks, the diabetic rats were assessed for neuropathy. Then, the diabetic rats with neuropathy were randomly divided into 6 groups for a 4-week treatment with gabapentin, oral administration of C. colocynthis fruit pulp powder (100 and 300 mg/kg per day), topical preparations as oil-based solution and ointment, or placebo. Changes in metabolic, physiological, biochemical and histological parameters were considered as treatment outcomes. RESULTS: Metabolic outcomes (body weight and blood glucose level) were improved in the C. colocynthis-treated groups as compared to placebo. Tail-flick and hot-plate tests also had lower latency in the C. colocynthis-treated groups. Measurement of oxidative stress markers (malondialdehyde, superoxide dismutase and catalase) showed the antioxidant effect of C. colocynthis. Histological evaluation of the sciatic nerve showed that C. colocynthis decreased the number of demyelinated and degenerated nerve fibers. Among the C. colocynthis-treated groups, the one receiving 100 mg/kg power per day orally had the best treatment outcomes. CONCLUSION: The present study showed that C. colocynthis fruit, through its antioxidant and hypoglycemic activities, has a positive effect in the treatment of diabetic neuropathy.

The Association Between Prolonged Proton Pump Inhibitors Use and Bone Mineral Density.

BACKGROUND AND STUDY AIM: Chronic use of proton-pump inhibitors (PPIs) has become a mainstay of therapy in common gastrointestinal diseases. A causal relationship between chronic PPI use and development of osteoporosis remains unproven. The aim of this study was to determine whether PPI users are more likely to develop alterations in bone density. PATIENTS AND METHODS: In an analytical cross sectional study, patients who used PPIs for more than 2 years because of long-term gastroesophageal reflux disease (GERD) were recruited. PPI users were healthy people except for GERD. The compression group was randomly derived from an age-, sex- and physical activity-matched group from a healthy population in the National Registry of Osteoporosis who had not used PPIs in the previous 2 years. Bone mineral density was measured with dual-energy X-ray absorptiometry. Data regarding BMD and bone mineral content (BMC) of three regions: femoral neck, total hip, and the lumbar spine (L1-L4) were gathered and recorded. The World Health Organization (WHO) classification was used for definition of osteopenia and osteoporosis. RESULTS: A total of 394 participants (133 PPI users and 261 comparison group) were enrolled. The median duration of PPI use was 6.7 (2-31) years. The mean age ± SD of PPI users and comparison group was 48.38 ± 11.98 and 47.86 ± years, respectively (P = 0.681). There was no significant difference in baseline characteristics and age distribution between the two groups. The BMC levels were significantly lower in PPI users in all three regions: lumbar spine, total hip, and femoral neck (P<0.001). There were no significant differences in the T-scores between the two groups except for femoral neck (P<0.001). Osteoporosis in femoral neck was significantly higher in PPI users than in comparison group. CONCLUSION: This study showed that long-term use of PPIs is associated with lower BMC and higher rate of osteoporosis in the femoral neck. However, more studies with longitudinal evaluation should be performed to clarify this causal relationship. Until then, it is advised not to overuse PPIs because of the possible increase in risk of osteoporosis and the risk of fractures. We also recommend using the BMC levels as a quantitative measure in addition to T scores in analysis and reporting similar studies.