A. R. Dehpour, PharmD, PhD
A. Javadian, MD
Vol 56, No 4 (2018)
Ankylosing spondylitis (AS) is a chronic immune-mediated inflammatory arthritis of unknown etiology, which belongs to a group of conditions known as spondyloarthropathies that comprises psoriatic arthritis, reactive arthritis, and enteropathic arthritis. AS causes pathologic new-bone formation in the axial skeleton, and leads to chronic pain, axial fusion, deformity, disability and skeletal fracture. Several genetic and environmental factors are known to be associated with AS. Notwithstanding the fact that a multitude of genes, such as human leukocyte antigen B27 (HLA-B27), endoplasmic reticulum-associated aminopeptidase 1 (ERAP1), and interleukin-23 receptor (IL-23R) have been previously speculated to be associated with individuals’ susceptibility to AS, no consensus about their precise role in the etiopathogenesis of AS has been reached. In the present study, we summarize the current literature on the immunogenetics of AS and contemporize the research advancement that has been made over the past decade.
Peripheral neuropathy, regularly expressed as hypersensitivity to painful stimuli, is between the most common complications of spinal cord injury (SCI) that develops in up to 40% of patients and appears to be persistent. Previous studies have demonstrated neuroprotective effects of Granulocyte colony-stimulating factor (G-CSF) on neuropathic pains. We aimed to investigate the antihyperalgesic effect of G-CSF on neuropathic pains following SCI in male rats. Twenty four adult male rats (weight 300–350g) were used. After laminectomy, complete SCI was performed by compression of the spinal cord for 1 minute with an aneurysm clip. Within 30 minutes after the surgery, 200 µg/kg G-CSF was injected intravenously in G-CSF treated groups and then was repeated in 3 consecutive days. Tail flick latency (TFL), acetone drop test scores, BBB test scores, and Von-Frey filament test were performed before surgery and once a week after surgery. Rats in G-CSF treated group showed significantly higher mean TFL, and lower mean score of acetone test compared with those in SCI+veh group 4 weeks after surgery (P<0.05). There was no significant difference between rats in G-CSF treated group and SCI+veh group in BBB and Von-Frey filament tests results. These findings revealed that treatment with systemic administration of intravenous G-CSF would attenuate thermal hyperalgesia, and cold allodynia induced by SCI in rats but has no significant effect on locomotor activity and mechanical allodynia after SCI.
Numerous in vitro, in vivo and clinical studies have evidenced the outstanding potential of dihydrotestosterone (DHT) in the treatment of male osteoporosis. Despite of promising clinical efficacy of DHT in regulating the skeletal growth and homeostasis, the exact molecular and translational mechanism is yet to be explored. This study was aimed to investigate the bone-forming molecular mechanism of DHT using MC3T3-E1 cell line as in vitro model. The mechanism of bone-forming ability of DHT was assessed by evaluating the time-mannered expression of bone-related biomarkers such as bone morphogenic protein-2 (BMP-2), alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx-2), osteocalcin (OCN), type I collagen, osteopontin (OPN), transforming growth factor-β1 (TGF-β1) and androgen receptor (AR). Results demonstrated a remarkable efficacy of DHT (at a dose of 0.1 ng/mL) in promoting the expression of these vital bone-forming mediators. The resulting analysis revealed that the DHT-0.1 group showed higher expression of BMP-2 (106±9 pg/mL), ALP (381±16 pg/mL), Runx-2 (664±32 pg/mL), OCN (2265±111 pg/mL), type I collagen (276±16 pg/mL), TGF-β1 (81±7 pg/mL) and AR (411±21 pg/mL) compared to the control (CN) and other DHT-treated groups. These findings provide an in vitro evidence for the bone-forming capacity of DHT and its therapeutic significance for the treatment of male osteoporosis.
Gabapentin is popular analgesic adjuvants for improving postoperative pain management. The aim of this study was to compare the preventive effects of pre-emptive oxycodone and gabapentin on acute pain after elective abdominal hysterectomy. One hundred patients undergoing abdominal hysterectomy were randomly assigned to oxycodone group received 10 mg of oxycodone and gabapentin group received 10 mg of gabapentin 1 hour before surgery. The anesthetic technique was standardized, and the postoperative assessments included the amount of meperidine consumption, PONV and VAS for postoperative pain at arrival to recovery, 6, 12 and 24 h after surgery. Bleeding loss assessed during surgery. Postoperative pain scores were significantly lower in the gabapentin group compared with the oxycodone group. (P=0.0001) The total meperidine used in the gabapentin group was significantly less than in the oxycodone group. Postoperative nausea and vomiting (PONV) and blood loss during surgery were significantly decreased in gabapentin group. Based on the results of this study, Pre-emptive use of gabapentin 1200 mg orally, significantly decreases postoperative pain and PONV, rescues analgesic requirements and also bleeding loss during surgery in patients who undergo abdominal hysterectomy. Significant side effects were not observed.
To explore glycemic control, and adverse events of Iranian people with uncontrolled type 2 diabetes after initiation of long-acting basal insulin, glargine. People with uncontrolled type 2 diabetes that was on at least two oral anti-diabetic drugs (OAD) were enrolled in this observational prospective study. Insulin glargine was prescribed by physicians in the course of routine clinical practice. Patients were followed for 24 weeks. Insulin doses were titrated to reach fasting blood sugar (FBS) target between 90 mg/dl and 130 mg/dl. HbA1c and adverse events were recorded at baseline, week 12, and week 24. Form a total of 292 participants, 243 patients completed the study. HbA1c, FBS, postprandial glucose, total cholesterol, triglycerides, and low-density lipoprotein cholesterol, but not body mass index decreased during the study. The proportion of poorly controlled patients (HbA1C>9%) decreased from 172 (58.9%) to 39(13.4%), and 21(7.2%) during follow up. Controlled glycemia (HbA1C<7%) was detected in 7(2.4%), 48 (16.4%) and 56 (19.2%) of patients at baseline, week 12 and week 24. Hypoglycemia was reported in 5.1% and 3.4% of the participants in the week at 12 and 24, respectively. Patients felt more satisfied with their blood glucose control, timing and choices of meals, and hypo/hyperglycemic experiences. Insulin glargine initiation in people with uncontrolled type 2 diabetes on 2 OADs is associated with significant improvement in metabolic control. Insulin glargine has good safety profile and well tolerated by the patients.
Knee osteoarthritis (KOA) is prevalent morbidity which is associated with increased cardiovascular (CV) mortality. Any means to add to the risk stratification strategies especially prior to the total arthroplasty operations is of great applicability in terms of patient safety and cost reduction. We investigated the correlation between serum high sensitivity C-reactive protein (hs-CRP) levels, as a measure of CV risk, and common carotid intima-media thickness (IMT), as the cursor of underlying atherosclerosis. In a cross-sectional study, serum hs-CRP levels and common carotid IMT were determined in 68 patients with KOA. The mean serum hs-CRP level was 1.85±1.98 mg/L, and the mean carotid IMT was 0.67±0.16 centimeters with a Pearson’s R=0.016 (P=0.898). Using linear regression models, no correlation was found between hs-CRP and IMT. Findings indicate the poor ability of hs-CRP to predict underlying atherosclerosis in patients with KOA. Although hs-CRP has been shown to be a powerful prognostic tool in general and is associated with increased mortality in patients with KOA, its applicability to predict the atherosclerosis risk especially prior to operation is limited. Further investigation to find the best cost-effective non-invasive indicator of CV risk in patients with KOA is mandatory.
Congenital hypothyroidism (CH) is the most frequent type of endocrine disorders which presents at birth. It plays a major role in developing the most common preventable type of mental retardation around the world. In this study, we aimed to investigate CH incidence and its predictive factors among newborns in Yazd province. This cohort study was conducted in 38 health centers of 10 cities in Yazd province which is located in the center of Iran, from March 2008 to February 2015. All neonates, as the audiences of this program, were evaluated using heel prick or Guthrie test according to the national protocol of CH screening. During 7 years of screening for CH from March 2008 to February 2015, 143190 neonates were screened. Among them, 434 neonates were diagnosed as affected cases by CH, and the 7-year incidence of this disease was 303/ 100,000 live births. First, cousin consanguinity, hospitalization, male sex and low birth weight had a significant relationship with congenital hypothyroidism. Logistic regression analysis revealed that aforementioned variables in addition to delivery type (cesarean section) were significant predictor of CH. CH is more prevalent in Yazd compared to the other provinces in Iran. It is recommended that the effects of probable risk factors are evaluated through additional longitudinal studies and effective preventive strategies are designed according to the results.
A close association between thyroid problems and polycystic ovarian syndrome (PCOS) has been recently raised suggesting common pathophysiological link between the two disease conditions. The present study aimed to assess the status of thyroid hormones in women with PCOS with the aim of clarifying the link between PCOS and thyroid abnormalities. This cross-sectional study was performed on 87 consecutive women aged 31 to 50 years finally diagnosed as PCOS based on the Rotterdam diagnostic criteria. Venous blood sample was extracted from all subjects to determine the levels of fasting blood glucose, hemoglobin A1C, serum insulin level and also thyroid hormones in a single laboratory. The mean serum level of TSH was 3.02±1.19 µIU/ml, the mean level of T4 was 7.22±1.81 µg/dl, and the mean level of T3 was 1.23±0.18 ng/ml. Based on the normal values of thyroid hormones, none of the PCOS patients had abnormal levels of TSH and T3 hormones. Also, normal level of T4 was revealed in 90.8% of patients, while only 6.9% and 2.3% had T4 level lower than and higher than the normal range respectively. Using the correlation tests, none of the thyroid hormones was linearly associated with age, weight, BMI, the value of FBS or the levels of lipid profiles. The high prevalence rate of overweight to obesity (97.7%), hypertriglyceridemia (65.5%), and uncontrolled glycemic status (21.8%) were prominent in PCOS women. In our observation, we found no significant link between abnormal changes in thyroid hormone and PCOS.
Cavernous hemangioma of the colon is a rare vascular malformation but is clinically important because it can sometimes cause massive bleeding. We report a case of thrombocytopenia in a post-partum young woman with large cavernous hemangioma of the ileum and colon, culminating in Kasabach Merritt syndrome (KMS), massive uncontrollable hemorrhage, and death. CT scan shows multiple submucosal bulgings in all segments of the colon. Macroscopic examination showed multiple well-defined masses, with gray-brown color in ileum, cecum and ascending colon. The masses were found to be a cavernous hemangioma with a thick fibrotic wall and extensive intra-cystic hemorrhage. KMS is an uncommon complication of colonic large hemangiomas that, as in our patient, can lead to uncontrollable bleeding and death and should be kept in mind by visceral surgeons as one differential diagnosis of large intra-abdominal tumorous masses, especially in young adults.
Berardinelli-Seip congenital lipodystrophy (BSCL) is an autosomal recessive disorder, characterized by the generalized absence of subcutaneous fat and muscular hypertrophy. Meanwhile other signs and symptoms have already been reported with this genetic disorder. Herein, we report an infant with BSCL, who was referred to our center because of acromegaloid and muscular appearance from the age of three months. He had dark skin, hypertrichosis prominent subcutaneous vessels and organomegaly in physical examination. Genetic study showed novel homozygous mutations in the AGPAT2 gene, which confirmed diagnosis of BSCL in this patient. Although clinical suspicious could help us to make diagnosis of congenital disorders, definite diagnosis relies on genetic studies.
Warfarin-induced Breast necrosis (WIBN) is an exceedingly rare sequel to warfarin therapy. A close relationship was confirmed between congenital deficiency of protein C and S and warfarin usage. A predilection for this complication has been reported in fatty middle-aged women who are managing by warfarin. The sudden eruption of the bullous lesion, within mean three days after starting of warfarin therapy with or without echymous or petechia is the first sign of WIBN. The maintenance of INR in the low normal range, reducing the loading doses, especially in fatty cases may be a preventive measure in reducing risk and incidence of breast necrosis in the high-risk subjects. Early diagnosis and management are important to prevent significant tissue loss. A rare case of warfarin-related necrosis of the left breast following a mitral valve replacement is reported. Current knowledge and the preventing methods and treatment of this rare complication are reviewed.
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