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Effect of weight reduction on histological activity and fibrosis of lean nonalcoholic steatohepatitis patient

Abstract

Background and Objectives

Weight reduction has evidenced benefit on attenuation of histological activity and fibrosis of nonalcoholic steatohepatitis (NASH), but there is scarcity of data for lean NASH subgroup. We have designed this study to compare the effects of weight reduction on histological activity and fibrosis of lean and non-lean NASH.

Methods

We have included 20 lean and 20 non-lean histologically proven NASH patients. BMI < 25 kg/m2 was defined as non-lean. Informed consent was taken from each subject. All methods were carried out in accordance with the Declaration of Helsinki. Moderate exercise along with dietary restriction was advised for both groups for weight reduction. After 1 year, 16 non-lean and 15 lean had completed second liver biopsy.

Results

Age, sex, alanine transaminase (ALT), aspartate aminotransferase (AST), gamma-glutamyltrasferase (GGT), Homeostasis model assessment insulin resistance (HOMA-IR), triglyceride and high density lipoprotein (HDL) was similar in both groups. Steatosis, ballooning, lobular inflammation, nonalcoholic fatty liver disease activity score (NAS) and fibrosis was similar in the two groups. In lean/non-lean group, any amount of weight reduction, ≥ 5% weight reduction and ≥ 7% weight reduction was found in respectively 8/11, 5/6 and 2/6 patients. In both lean and non-lean groups, weight reduction of any amount was associated with significant reduction of steatosis, ballooning and NAS, except lobular inflammation and fibrosis. In both groups, weight reduction of ≥ 5% was associated with significant reduction in NAS only. However, significant improvement in NAS was noted with ≥ 7% weight reduction in non-lean group only.

Conclusion

Smaller amount of weight reduction had the good benefit of improvement in all the segments of histological activity in both lean and non-lean NASH.

Open access
Elevated lactic acid during ketoacidosis: pathophysiology and management

Abstract

Lactic acidosis results from an acid-base balance disorder of the body due to an excess of lactic acid. It is frequently found in critically ill patients admitted to the intensive care. The most common cause is type A, found in pathologies such as cardiogenic, septic and hypovolemic shock, trauma and severe hypoxemia. The type B is less common and arises without evidence of tissue hypoperfusion or shock. Divers etiologies have been described for this type of hyperlactatemia: Grand Mal seizures, liver failure, hematologic malignancies, congenital enzyme deficiencies, thiamine deficiencies and diabetes mellitus and also alcohol abuse, which may induce a lactic acid under-use or an increased production. The authors describe a rare complication of type 1 Diabetes Mellitus (T1DM), leading to a major and persistent expression of a type B lactic acidosis during ketoacidosis.

Open access
Endoscopic Ultrasound-guided Gastroenterostomy: A Promising Alternative to Surgery

Abstract

Recently, with the advancement of techniques, endoscopic ultrasound-guided therapies have shown distinct advantages, especially in relieving benign and malignant gastric outlet obstruction (GOO), as well as in postoperative pancreaticobiliary diseases. Herein, we present five currently used approaches in endoscopic ultrasound-guided gastroenterostomy (EUS-GE) using lumenapposing biflanged metal stents (LAMS), along with several examples of LAMS-based EUS treatment of pancreaticobiliary diseases. Compared with traditional treatment methods, EUS-guided procedures have – to some degree – shown higher success rates, both technical and clinical. Moreover, EUS-guided therapies reduce the risk of multiple surgical adverse events, including delayed gastric emptying, prolonged hospital stay, increased costs, and delay in cancer treatment. Particularly in terms of postoperative pancreaticobiliary diseases, EUS-guided therapy has assumed an essential role as a treatment option in cases where traditional methods are difficult to perform. Nevertheless, EUS-guided gastrointestinal procedures are still relatively new, with some clinical failures, and additional prospective clinical trials are warranted.

Open access
Treatment of ventilator-associated pneumonia with high-dose colistin under continuous veno-venous hemofiltration

Abstract

Background and Objectives

High-dose colistin (COL) ensures adequate treatment of pneumonia caused by multidrug resistant gram-negative bacteria (MDR-GNB) but must be weighed against a higher risk of nephrotoxicity. Continuous veno-venous hemofiltration (CVVH) clears COL by filtering and membrane adsorption that permits to avoid dose accumulation and excessively high peak concentrations. We evaluated clinical/microbiological efficacy of the high-dose COL treatment under CVVH in patients with newly diagnosed MDR-GNB ventilator-associated pneumonia (VAP).

Methods

Observational cohort study in critically ill adult patients with MDR-GNB VAP. Colistimethate sodium (CMS) was administered as a 9 million international units (MIU) of loading dose followed by 3 × 4.5 MIU daily. CVVH was performed over a highly adsorptive membrane. Clinical and microbiological efficacies were assessed at the end of therapy. In survivors, serum creatinine level was evaluated before and at the end of therapy.

Results

Fourteen patients (8 male patients, aged 57 ± 14 years) were consecutively included. Isolated pathogens were Pseudomonas aeruginosa in 7, Klebsiella pneumoniae in 5, and other Enterobacteriaceae in 2 patients. A favorable clinical response was observed in 9 patients (64%). Full and presumed microbiological eradication was observed in 12 patients (86%). Two patients were diagnosed with Stage 1 acute kidney injury.

Conclusions

In patients with MDR-GNB VAP, CVVH may represent an interesting option to enable effective high-dose COL treatment.

Open access
The bone hormones and their potential effects on glucose and energy metabolism

Abstract

The bones form the framework of our body. We know that bones protect our vital organs, regulate calcium and phosphorous homeostasis, and function as a site of erythropoiesis. More recently, however, the identification of bone hormones has allowed us to envision bones as endocrine organs too. Within the last few years, the bone hormones osteocalcin and lipocalin 2 have been implicated with glucose and energy metabolism. We systematically reviewed articles surrounding this subject and found a clear relationship between the osteocalcin levels and glucose tolerance and insulin sensitivity. We also found that many journals have shown the detrimental effects of an absences of lipocalin 2 from adipocytes. As osteocalcin administration to mice showed decreased blood glucose levels and promoted glucose tolerance and insulin sensitivity. Future studies could perhaps explore the use of osteocalcin as a supplement for type 2 diabetes.

Open access
The coexistence of infundibular pituicytoma and Cushing’s disease due to pituitary adenoma: A case report

Abstract

Objectives. Pituicytomas are rare, solid, well-circumscribed, low grade (grade I), non-neuroendocrine, and noninfiltrative tumors of the neurohypophysis or infundibulum, which appear in the sellar/suprasellar regions. Herein, we present a case with Cushing’s disease (CD) caused by an ACTH-secreting pituitary adenoma in association with an infundibular pituicytoma.

Subject and Results. A 37-year-old male patient presented to the hospital with a six-month history of blurry vision. Physical examination demonstrated plethora, excessive sweating, weight gain, moon facies, and acne. Basal serum cortisol and ACTH levels were 16 µg/dl and 32 pg/ml, respectively. The results of screening tests were suggestive of Cushing syndrome. It was also 1.97 µg/dl following 8 mg dexamethasone suppression test which was consistent with CD. Pituitary MR imaging revealed a single lesion measuring 6x6.5 mm on the pituitary stalk. Infundibular mass excision and pituitary exploration by extended endoscopic endonasal approach were applied. On immunohistochemistry, strong diffuse immunolabeling for both S100 and TTF-1 was noted for the cells of infundibular mass, diagnosed as pituicytoma. Because the developed panhypopituitarism postoperatively, patient was discharged with daily desmopressin, levothyroxine, hydrocortisone, and intramuscular testosterone, once a month.

Conclusions. Pituicytoma is an uncommon noninvasive tumor of the sellar and suprasellar regions. In this case report, we described a patient with Cushing’s disease to whom MRI displayed only an infundibular well-circumscribed lesion, but not any pituitary adenoma. Despite the absence of any sellar lesion, awareness of other undetected possible lesion and exploring hypophysis during the transsphenoidal surgery is mandatory for the correct diagnosis.

Open access
Comparing the preventive effect of sodium hydrosulfide, leptin, and curcumin against L-arginine induced acute pancreatitis in rats: role of corticosterone and inducible nitric oxide synthase

Abstract

Objectives. Acute pancreatitis (AP) is a life-threatening condition. Using antioxidants in AP is insufficient and conflicting. Therefore, this study compared the effect of hydrogen sulfide (H2S) donor, sodium hydrosulfide (NaHS), leptin or curcumin pretreatment on AP induced by L-arginine.

Methods. Forty adult male rats were used and classified into: 1) control; 2) AP group [each rat was intraperitoneally (i.p.) injected with 2 doses of L-arginine of 250 mg/100 g body weight (b.w.) with an interval of 1 h]; 3) NaHS+AP group (each rat was i.p. injected with 10 mg/kg b.w. of NaHS 1 h before induction of AP); 4) leptin+AP group (each rat was pretreated with 10 μg/kg b.w. of leptin 30 min before induction of AP; and 5) curcumin+AP group (in which rats were i.p. injected with 150 mg/kg b.w. of curcumin 30 min before induction of AP). Serum amylase, lipase, nitric oxide (NO), tumor necrosis factor alpha (TNF-α), and corticosterone (CORT) levels were assayed. In addition, pancreatic tissues were obtained for histopathological examination and malondialde-hyde (MDA), total antioxidant capacity (TAC), and inducible nitric oxide synthase (iNOS) levels were measured.

Results. All AP treated groups showed significant decrease in serum levels of pancreatic enzymes, NO, and TNF-α, and pancreatic MDA and iNOS levels, while TAC levels were significantly increased. NaHS caused more limitation of inflammation than leptin and curcumin by affecting iNOS. Leptin was more potent than curcumin due to the stimulatory effect of leptin on glucocorticoid release to counteract inflammation.

Conclusions. NaHS was more effective in AP amelioration than the leptin and curcumin.

Open access
Early postnatal hypothalamic-pituitary-adrenal axis activity and reduced insulin sensitivity in adult rats

Abstract

Objective. Early life stress influences the development of metabolic disorders, including functional changes in the developing of pancreas mediated hypothalamic-pituitary-adrenal (HPA) axis. In the present study, the role of an early postnatal stress on corticosterone, glucose, and insulin levels was investigated during young adulthood.

Methods. Two groups of pups were studied, including control group (pups not receiving foot shock by communication box), and early stress group (pups receiving foot shock by communication box 2 times/day for 5 consecutive days). In rats, concentration of plasma corticosterone, glucose, and insulin was detected before and after placing them into the communication box at 2 weeks of age. At 8–10 weeks of age, concentrations of plasma corticosterone, glucose, and insulin and glucose tolerance were measured in young adult rats.

Results. Our results showed that early postnatal foot shock stress increased the corticosterone, insulin, and glucose levels in the postnatal age (p<0.01) that did not last until young adult age, but it caused a significant increase in plasma glucose and insulin levels (p<0.05) following the intraperitoneal glucose tolerance test (IPGTT) in young adult rats.

Conclusions. These results suggest that impaired IPGTT in young adult rats who experienced early postnatal stress can indicate insulin resistance or reduced insulin sensitivity that make it at risk of the type 2 diabetes later in life.

Open access