Hypoglycemic and antioxidant effect of Juniperus procera extract on rats with streptozotocin-induced diabetes

Juniperus procera, a coniferous tree in the cypress family, is one of the famous medicinal plants traditionally used in the southern area of the Arabian peninsula. This study examined the anti-hyperglycemic action of Juniperus procera extract (JPE) on diabetic rats. Sixty male rats were divided into 6 equal groups: control, control treated with JPE (200 mg/kg), diabetic, diabetic treated with insulin (1 U/kg), diabetic treated with JPE (200 mg/kg), and diabetic treated with both insulin and JPE. Blood and tissue samples were collected for serum chemistry, gene expression, and immunohistochemistry analyses, the results of which revealed hyperglycemia and inflammation following diabetes induction. Administration of JPE alone or with insulin reduced the hyperglycemia reported in diabetic rats by 25 %. The immunohistochemical examination of pancreatic tissues demonstrated a moderate restoration of insulin and NF-κB expression in pancreatic and hepatic tissues. Significant recovery was observed for glutathione-S-transferase (GST), superoxide dismutase (SOD), and glutathione peroxidase (GPx) mRNA expression in the livers of rats treated with JPE. Administration of JPE led to similar amelioration of the mRNA expression of pyruvate kinase (PK) and phosphoenol pyruvate carboxy kinase (PEPCK) in the livers of diabetic rats. In addition, diabetic rats treated with insulin, JPE, or a combination of these agents demonstrated an improvement in the mRNA expression of IRS-1 and IRS-2 in hepatic and pancreatic tissues, reaching levels approaching normal. Our findings led us to conclude that JPE has a powerful anti-inflammatory effect accompanied by a moderate hypoglycemic effect that occurs via different mechanisms.     

Long-term clinical and radiological outcomes after multiligament knee injury using a delayed ligament reconstruction approach: A single-center experience

PurposeTo present long-term clinical and radiological results of patients treated with delayed reconstruction of multiligament knee injuries.MethodsClinical data from 26 patients (21 men, five women, mean age 27.44 years) were retrospectively reviewed. Patients were evaluated at final follow-up with the use of: The International Knee Documentation Committee score (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS), Tegner Activity level, Lysholm Knee Scoring Scale, EuroQol subjective knee evaluation form, and KT-2000 arthrometer. Mean follow-up time was 105.38 months. Both knees were radiographically evaluated for osteoarthritis according to the Kellgren–Lawrence classification.ResultsNo patient required mobilization under anesthesia for adhesion lysis at the immediate or later postoperative duration. There was no statistically significant difference in range of motion between the healthy and operated sides (P = 0.713). Mean time to final range of motion regain was 2.1 ± 0.4 months. Average KT-2000 side-to-side (operated vs. normal) difference was 2.03 ± 1.1 mm, and the difference was statistically significant (P = 0.007). The mean IKDC, KOOS, Lysholm, Tegner, and Euroqol-5D postoperative scores were 82.13 ± 17.5, 84.59 ± 16.8, 90.6 ± 6.4, 4.3 ± 1.3, and 80 ± 11.74, respectively. Multiple regression analysis showed that age and follow-up time had significant effects on each clinical score, except for the Lysholm and Tegner scores. Progression of osteoarthritic changes of the reconstructed knee and its contralateral side was significantly different (P = 0.003).ConclusionExcellent clinical results were reported from this center's long-term experience with delayed ligament reconstruction, and osteoarthritic changes of reconstructed knees were recorded.     

Rapidly growing non-tuberculous mycobacteria infection of prosthetic knee joints: A report of two cases

Non-tuberculous mycobacteria (NTM) cause prosthetic knee joint infections in rare cases. Infections with rapidly growing non-tuberculous mycobacteria (RGNTM) are difficult to treat due to their aggressive clinical behavior and resistance to antibiotics. Infections of a prosthetic knee joint by RGNTM have rarely been reported. A standard of treatment has not yet been established because of the rarity of the condition.In previous reports, diagnoses of RGNTM infections in prosthetic knee joints took a long time to reach because the condition was not suspected, due to its rarity. In addition, it is difficult to identify RGNTM in the lab because special identification tests are needed. In previous reports, after treatment for RGNTM prosthetic infections, knee prostheses could not be re-implanted in all cases but one, resulting in arthrodesis or resection arthroplasty; this was most likely due to the aggressiveness of these organisms. In the present report, two cases of prosthetic knee joint infection caused by RGNTM (Mycobacterium abscessus) are described that were successfully treated, and in which prosthetic joints were finally reimplanted in two-stage revision surgery.     

Mucormycosis in Iran: A six-year retrospective experience

Mucormycosis is a devastating infection caused by Mucoralean fungi (Mucormycotina, Mucorales). Data concerning the global epidemiology of mucormycosis are scarce and little is known about the characteristics of mucormycosis in Iran. In this study, we aimed to understand the distribution of this infection in Iran retrospectively and to ascertain whether the patterns of infection are associated with specific host factors or not. A total of 208 cases were included in this study occurring during 2008–2014 and were validated according to (EORTC/MSG) criteria. A rising trend as significant increase from 9.7% in 2008 to 23.7% in 2014 was observed. The majority of patients were female (51.4%) with median age of 50 and the infections were seen mostly in autumn season (39.4%). Diabetes mellitus (75.4%) was the most common underlying condition and sinus involvement (86%) was the mostly affected site of infection. Amphotericin B (AmB) was the drug of choice for the majority of cases. Sixty four isolates did not show any growth in the lab and only 21 cases were evaluated by ITS sequencing, among them; Rhizopus arrhizus var. arrhizus was the dominant species. Considering the high mortality rate of mucormycosis, early and accurate diagnosis, with the aid of molecular methods may provide accurate treatments and improve the survival rate. Therefore, increased monitoring and awareness of this life-threatening disease is critical.     

Split hand-foot malformation and a novel WNT10B mutation

We report an Indian girl with split-hand/foot malformation (SHFM), sparse hair, and interrupted eyebrows, who carries a novel homozygous deletion c.695_697delACA in WNT10B. The variant is deduced to cause an in-frame deletion of Asn residue 232 (p.Asn232del). According to the protein model, this single amino acid deletion at the critical position in the protein structure is likely to severely affect the protein structure and function. This deletion is likely to lead decreased lifetime and make it unable to bind to its receptors and other ligands. The patient and all family members had normal bone density and they were not obese like some of the patients with WNT10B variants. Here we report a patient with SHFM6 who carried a novel WNT10B mutation. Sparse hair and interrupted eyebrows may be associated findings of SHFM6.     

A case of Woodhouse-Sakati syndrome with pituitary iron deposition,cardiac and intestinal anomalies,with a novel mutation in DCAF17

Woodhouse-Sakati syndrome is a rare genetic syndrome caused by homozygous mutations of the DCAF17 gene. Several endocrine organs may be affected in the course of the disease. We present a new case with pituitary iron deposition, cardiac and intestinal anomalies, with a novel mutation in DCAF17 gene. An 18-year-old female was admitted because of delayed puberty and amenorrhea. Hormonal evaluation revealed combined hyper-hypogonadotropic hypogonadism. GH and IGF-1 levels were low without short stature. ACTH levels were high and cortisol levels were supranormal with the lack of clinical findings of cortisol excess or deficiency. Pituitary MRI indicated paramagnetic substance deposition in gland. On follow-ups, non-autoimmune, insulinopenic diabetes mellitus and secondary hypothyroidism emerged. Woodhouse-Sakati syndrome was diagnosed on the basis of consistent clinical context and subsequently a novel mutation in DCAF17 was detected.     

Amyloidosis secondary to chronic pulmonary aspergillosis: Case report and a systematic review of literature

Secondary amyloidosis results from the deposition of abnormally folded proteins in body organs due to chronic inflammatory disorders. Kidneys are the most commonly affected organ and manifest as nephrotic syndrome with or without renal failure. Chronic pulmonary aspergillosis (CPA) is a chronic infection of lung parenchyma affecting those with an underlying structural lung disease. Herein, we present a case of CPA where the initial manifestation was that of nephrotic syndrome due to renal amyloidosis. We also perform a systematic review for studies describing secondary amyloidosis due to CPA.     

Gastric adenocarcinoma with enteroblastic differentiation should be differentiated from hepatoid adenocarcinoma: A study with emphasis on clear cells and clinicopathologic spectrum

BackgroundIn gastric cancer, clear cells are preferentially found in gastric adenocarcinoma with enteroblastic differentiation (GAED) and hepatoid adenocarcinoma (HAC). The distinction between GAED and HAC is difficult because of their rarity and histologic overlap.MethodsTo elucidate identification of gastric adenocarcinoma with clear cells as GAED or HAC, survival analyses were performed in 28 GAED, 26 HAC, and 1107 conventional adenocarcinoma cases. Cells of origin were assessed by investigating the expression of oncofetal proteins (α-FP, glypican-3, SALL4), in addition to gastric (MUC5AC, MUC6), and intestinal (MUC2, CD10, CDX-2) cell markers.ResultsClinically, HAC showed frequent (57.5%) distant metastasis (mostly in the liver) at the time of diagnosis compared to GAED (P < 0.001). On pathology, all 28 GAED had a predominantly tubulopapillary growth pattern while 24 HAC displayed a predominantly hepatoid growth pattern. In survival analyses, patients with HAC had significantly shorter overall and recurrence-free survival (mean: 25 months, and 53 months, respectively) compared to those with GAED (mean: 107 months, and 118 months, respectively) (P < 0.001).HAC with clear cells showed diffuse and strong expression of all oncofetal proteins (α-FP, glypican-3, and SALL4), were highly positive for CDX-2, and were negative for CD10, MUC6, MUC5AC, and MUC2, suggesting an intestinal mucin phenotype and hepatoid features. In contrast, GAED showed focal expression of one or two oncofetal proteins and commonly expressed CD10, CDX-2, and MUC6 but not MUC2 and MUC5AC, suggesting both gastric antral/intestinal mucin phenotype and focal enteroblastic differentiation. SALL4 was diffusely and strongly positive in HAC, while it was heterogeneously expressed in GAED.ConclusionsIn conclusion, although rare, HAC with clear cells should be differentiated from GAED based on the poor prognosis, diffuse and strong oncofetal protein expression, and intestinal mucin phenotype.     

Galectin-3 may serve as a marker for poor prognosis in colorectal cancer: A meta-analysis

Galectin-3 has an important function in the development of tumors. The purpose of this meta-analysis was to explore the relationships between the expression of galectin-3 on clinicopathological features and prognosis of colorectal cancer (CRC). A comprehensive literature search was used to identify eligible studies, and Stata software was conducted using in this meta-analysis. A total of 15 studies, including 1661 cases, were matched in the inclusion criteria. The pooled analysis indicated that galectin-3 expression was related to the poor overall survival (OS) in CRC patients (HR: 1.77, 95% CI: 1.36–2.31, P < 0.0001). Our meta-analysis also showed that cancerous tissues have higher levels of galectin-3 expression than normal tissues. Besides, positive galectin-3 expression was also related to advanced TNM stages(III/IV vs. I/II: OR 5.30, 95% CI: 2.42–11.61, P < 0.0001), higher Duke’s stages (C/D vs. A/B: OR 4.00, 95% CI: 2.22–7.22, P < 0.0001), venous invasion (venous invasion vs. not: OR 3.02, 95%CI: 1.75–5.22, P < 0.0001) and higher CEA level (CEA≥5 ng/ml vs. ≤ 5 ng/ml: OR 2.09, 95% CI: 1.09–4.03, P = 0.03). In summary, our results indicated that overexpression of galectin-3 is significantly related to the tumor progression and could be a efficient in predicting the prognosis of patients with CRC.     

Allergic fungal rhinosinusitis caused by Neoscytalidium dimidiatum: A case report: Allergic fungal rhinosinusitis due to Neoscytalidium dimidiatum

Neoscytalidium dimidiatum is a rare dematiaceous fungus that was first described in 1916 as Dothiorella mangiferae. From the standpoint of epidemiology and therapy, early detection of fungal rhinosinusitis (FRS), the causative agents, and their associated risk factors can improve the therapeutic outcome and decrease the mortality rates among patients. In this study, we report a 34-year-old Iranian female patient with allergic bronchopulmonary aspergillosis (ABPA), who presented to our facility with an 8-year history of chronic fungal sinusitis, drug-resistant asthma, pneumonia, bronchitis, post-nasal discharge, nasal obstruction, nasal polyposis, and anemia. The patient was subjected to diagnostic nasal endoscopy and computed tomography (CT) scan of paranasal sinuses, as well as routine, complementary mycological, and molecular methods, which confirmed the diagnosis of allergic fungal rhinosinusitis in patients with ABPA. Neoscytalidium dimidiatum was isolated from the sinus of the patient. Results of in vitro susceptibility tests indicated that the case isolate was susceptible to amphotericin B and itraconazole at concentrations which are commonly achieved in patients receiving recommended dosages for invasive mycoses (0.25 to 0.75 mg/kg of body weight daily for amphotericin B and 100 to 400 mg daily for itraconazole) and resistant in vitro to caspofungin, voriconazole, and posaconazole. The patient was successfully treated with amphotericin B / itraconazole + postoperative oral corticosteroids (OCS). Neoscytalidium dimidiatum infection should be considered as a possible additional factor in the etiology of AFRS, especially in immunocompromised patients.     

Impact of renal ischemia/reperfusion injury on the rat Kupffer cell as a remote cell: A biochemical,histological, immunohistochemical,and electron microscopic study

Almost all transplanted solid organs are exposed to some degree of ischemia-reperfusion (IR) damage. It is interesting to know that this IR damage affects various remote tissues including the liver and resulted in serious adverse effects. Liver injury triggers different responses of liver tissue especially Kupffer cells (KCs). The goal of this current study is to assess the biochemical and morphological changes of hepatic KCs after the induction of renal ischemia-reperfusion (RIR) and point out their role in remote liver injury after RIR.Sixteen male Sprague-Dawley rats were randomly divided into two equal groups: Group I; sham group. Group II; renal ischemia reperfusion (IR) group in which rats were exposed to renal ischemia for 45 min followed by renal reperfusion for 48 h. Three rats from each group were subjected to charcoal injection to evaluate KCs activity. Specimens of rat liver from each group were obtained and processed for biochemical, light microscopic and ultramicroscopic examination. The current results showed elevated serum levels of AST and ALT. The liver HGF-α protein expression increased in IR group compared to the sham group. In IR group, numerous charcoal labeled KCs were observed mainly localized around the central vein. Scanning electron micrographs showed complex primary and secondary foot process of the KCs. Ultrastructural study showed KCs with multiple cytoplasmic vacuoles, lysosomes and mitochondria, rough endoplasmic reticulum and ribosomes. Immuno-histochemical study showed more tumor necrosis factor-α (TNF-α) expression in KCs than the sham group. These results collectively demonstrated that renal IR produced biochemical and morphological changes in the liver KCs and theses cells might have a role in the remote liver injury after renal IR. This might be one of the mechanisms through which RIR affects the liver.     

Ongoing issues with the management of children with Constitutional Mismatch Repair Deficiency syndrome

Constitutional Mismatch Repair Deficiency (CMMRD) is a rare cancer predisposition syndrome, presenting in childhood, in which affected patients develop various malignancies such as hematological, gastrointestinal and central nervous system tumors. Although guidelines are being increasingly developed for surveillance and early detection of cancers in affected families, there are no clear recommendations regarding choice of therapy and very scarce information about tolerance to chemotherapy and radiation in these patients.We report the pedigree of a consanguineous family with four affected children. Although clinical and molecular tests confirm CMMRD, genetic testing revealed heterogeneous mutations. The index case developed severe toxicity from therapy for glioblastoma and T-cell leukemia and died from an infection while in complete remission. His sister developed a malignant brain tumor while undergoing surveillance for a low grade brain lesion and is still undergoing follow-up.This family illustrates the difficulties and opportunities with challenging diagnosis, surveillance and choice of therapy for children with CMMRD and the need for increased awareness and more information about this rare but important syndrome.     

Atopic disorders in CHARGE syndrome: A retrospective study and literature review

Background

Atopic disorders have been reported in CHARGE syndrome, but the prevalence and underlying mechanisms are not known.

L-arginine supplementation lowers blood pressure,protein excretion and plasma lipid profile in experimental salt-induced hypertension in pregnancy: Relevance to preeclampsia

This study aimed to investigate the effects of L-arginine supplementation on blood pressure, protein excretion, lipid profile in salt-induced hypertensive pregnant rats.Female Sprague-Dawley rats were divided into 4 groups. Control Preg (normal rat chow). Control Preg + L-ARG (normal rat chow and daily oral L-Arginine from 16th – 20th week). Salt Preg (high salt diet, 8%). Salt Preg + L-ARG (high salt diet, 8% and daily oral L-Arginine from 16th – 20th week. Non-invasive BP was recorded using a tail-cuff machine at 1 st and 2nd trimesters. On day 19 of pregnancy, invasive BP was obtained by carotid artery cannulation connected to LabChart-7 pro software. This was followed by blood samples collection for lipid profile analysis.L-arginine significantly reduced (P < 0.05) systolic, diastolic, MAP at 1 st, 2nd trimesters, day 19 of pregnancy, LDL, plasma and urinary creatinine and protein levels in Control Preg + L-ARG and Salt Preg + L-ARG groups compared to other groups. Urinary Na + and K + were significantly higher (P < 0.05) in Salt Preg + L-ARG group compared to other groups. Total cholesterol level was significantly higher (P < 0.05) in salt groups compared to control groups. Triglyceride level and urine volume were significantly higher (P < 0.05) in Salt Preg group compared to other groups. It also significantly increased (P < 0.05) HDL in Control Preg + L-ARG and Salt Preg + L-ARG groups compared to other groups. L-arginine supplementation ameliorates some deleterious effects in salt- induced hypertensive pregnant rats possibly through its known NO vasodilatory effect and might also mediate a diuretic like action.