Theoretical and Experimental Evaluation of Flow Pattern of Pharmaceutical Powder Blends Discharged From Intermediate Bulk Containers (IBCs)

The purpose of this study is to assess the prevalence of funnel flow pattern for common pharmaceutical powder blends, upon discharging from modern intermediate bulk containers (IBCs) in drug product manufacturing. The estimation was built upon Jenike’s original radial stress field theory. It was modified to account for the stress-dependence of wall friction angle commonly observed in pharmaceutical powders. A total of 260 flow pattern estimations, based on 20 real-life IBCs and 13 investigational powder blends, were made. The estimated results showed that the mass flow pattern is present in less than 5% of all cases. Funnel flow pattern is clearly prevalent among pharmaceutical powder blends. The prevalence of funnel flow stems from several factors: 1) relatively shallow hopper section shared by all IBCs, 2) the common transition-type geometry, leading to even shallower hopper inclination at the edge of the hopper section, and 3) relatively high wall friction angles resulting from low wall normal stresses. This conclusion was verified through at-scale experiments, by discharging multiple pharmaceutical powder blends from a representative IBC. In general, our study suggests that, unless the powder wall friction can be substantially reduced, pharmaceutical powders are likely to discharge under funnel flow from modern IBCs.     

Eruptive Melanocytic Nevi: A Review

Eruptive melanocytic nevi (EMN) is a phenomenon characterized by the sudden onset of nevi. Our objective was to compile all published reports of EMN to identify possible precipitating factors and to evaluate the clinical appearance and course. We conducted a systematic bibliographic search and selected 93 articles, representing 179 patients with EMN. The suspected causes were skin and other diseases (50%); immunosuppressive agents, chemotherapy or melanotan (41%); and miscellaneous, including idiopathic (9%). The clinical manifestations could largely be divided into two categories: EMN associated with skin diseases were frequently few in number (fewer than ten nevi), large, and localized to the site of previous skin disease, whereas those due to other causes presented most often with multiple small widespread nevi. In general, EMN seem to persist unchanged after their appearance, but development over several years or fading has also been reported. Overall, 16% of the cases had at least one histologically confirmed dysplastic nevus. Five cases of associated melanoma were reported. We conclude that the clinical appearance of EMN may differ according to the suggested triggering factor. Based on the clinical distinction, we propose a new subclassification of EMN: (1) widespread eruptive nevi (WEN), with numerous small nevi, triggered by, for example, drugs and internal diseases, and (2) Köbner-like eruptive nevi, often with big and few nevi, associated with skin diseases and most often localized at the site of previous skin disease/trauma. The nature of the data precluded assessment of risk of malignant transformation.

     

Add-on treatment with nebulized hypertonic saline in a child with plastic bronchitis after the Glenn procedure,

Plastic bronchitis (PB), although a rare cause of airway obstruction, has mortality rates up to 50% in children after Fontan-type cardiac surgery. We present the case of an 18-month-old female patient with PB following pneumonia. At 6 months of age, the patient underwent the Glenn procedure due to functionally univentricular heart. Fiberoptic bronchoscopy revealed complete blockage of the left bronchus by mucoid casts. Pharmacotherapy consisted of glucocorticosteroids, azithromycin, and enalapril maleate. The child also received nebulized 3% NaCl solution, which proved to be beneficial. In children submitted to Fontan-type procedures, physicians must be alert for PB, which can be triggered by respiratory tract infection.     

The surgical anatomy of the sural nerve: An ultrasound study

The aim of this study was (a) to examine the anatomy of the sural nerve (SN) in a sample of 30 patients and (b) to analyze the incidence of different origins of the SN, and the distance of the SN from planned arthroscopic portals. An ultrasound (USG) examination of the SN was performed bilaterally on thirty healthy patients with no history of surgery or trauma of the lower limb. The SNs were classified into six main types of pattern, with an additional category for new and unclassified types. Each of Types 1 and 3 had two subdivisions. The distances from the superior border of the calcaneal tuberosity to the three simulated arthroscopy portal sites (Z1, Z1.5, Z2) to the SN were measured. A total of 30 patients (n = 60 limbs) with an average age of 27 ± 7.5 years were examined and the SN was visualized in all cases. The most common origin was Type 3A, accounting for 30% of limbs. Type 2 was the second most common seen in 18.3%. The distances of the SN from arthroscopic portal placement sites above the lateral malleolus were 2.07 ± 0.39 cm at the Z1 portal, 2.15 ± 0.38 cm at Z1.5, and 2.28 ± 0.33 cm at Z2. The variability in the anatomy of the SN warrants the use of USG to locate it accurately, thus preventing iatrogenic injury when portals are placed for arthroscopy, improving proper administration of anesthesia, and helping to localize the nerve for graft harvesting. Clin. Anat. 31:450–455, 2018. © 2017 Wiley Periodicals, Inc.     

Rho kinase inhibition ameliorates cyclophosphamide-induced cystitis in rats

Naunyn-Schmiedeberg's Archives of Pharmacology - Hemorrhagic cystitis often develops in patients treated with cyclophosphamide (CYP). Studies have indicated that Rho kinase (ROCK) inhibitors...     

Body composition does not affect serum levels of cathelicidin LL-37 in elderly women with unipolar depression

Objectives: Antimicrobial peptides are components of the innate immune system. Cathelicidin LL-37 plays an important role in antimicrobial defense, exerts proinflammatory effect and strongly affects the immune system functioning. Our recent study revealed that serum concentration of LL-37 is increased in elderly women with depression. The aim of this study is to evaluate serum LL-37 levels in elderly women with depression and to compare them with non-depressed elderly women, matched for anthropometric and body composition parameters.

Methods: Forty women with unipolar depression and 23 non-depressed women (age ≥60 years) were included into the study. Anthropometric measurements and biochemical analyzes were performed. Concentration of LL-37 in serum was assessed using ELISA method. Body composition was measured using two methods: bioimpedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA).

Results: There was a statistically significant difference (p =.038) in serum LL-37 level between patients with depression (3.55?±?6.57?ng/mL) and control subjects (2.01?±?3.88?ng/mL). Apart from visceral adipose tissue mass (%) in the depression group, we found no associations between serum LL-37 and analyzed anthropometric or body composition parameters.

Conclusions: Results of this study indicate that with the exception of visceral adipose tissue, LL-37 serum levels are not affected by anthropometric or body composition parameters. The association between visceral adipose tissue and LL-37 may indicate that visceral fat could be responsible for the increased LL-37 production.     

Epithelioid hemangioendothelioma of the liver as a rare indication for liver transplantation

AIM: To investigate the indications and outcomes of liver transplantation for hepatic epithelioid hemangioendothelioma (HEHE).METHODS: Between 1989 and August 2013, in the Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, 1306 orthotopic liver transplantations (OLTx) were performed, including 72 retransplantations. Unresectable HEHE was an indication for OLTx in 10 patients (0.8% of primary OLTx), the mean age of the patients was 40.5 ± 13.3 years (range 23-65 years), and the male-to-female ratio was 2:8. Kaplan-Meier survival analysis in HEHE, hepatocellular carcinoma (HCC), and other OLTx recipients groups was performed. The differences in mortality were compared using the χ² test. A P-value < 0.05 indicated statistical significance.RESULTS: No concomitant liver disease was found in any patient. There was no neoadjuvant chemotherapy or radiotherapy. Liver function test results were normal in most of the patients. The levels of alpha-fetoprotein, carcinoembryonic antigen, and carbohydrate antigen 19-9 were normal. In immunohistochemical staining, the neoplastic cells were positive for factor VIII-related antigen, CD31, and CD34, which are endothelial cell markers, and negative for cytokeratin 19, cytokeratin 7, and HepPar-1. Nine patients were alive without tumor recurrence. One patient died 2 mo after OLTx due to septic complications. No morbidity was observed. Maximum follow-up was 11.4 years, with a minimum of 1 mo. The cumulative survival rate at the end of follow-up in HEHE patients was 87.5% compared with 54.3% in the HCC group and 76.3% in the other OLTx recipients group (χ² test = 1.784, df = 2, P = 0.409).CONCLUSION: Unresectable HEHE, without extrahepatic metastases is an excellent indication for liver transplantation. Long-term survival is very good and much better than in HCC patients and the entire group of OLTx patients.     

Enrichment of spreadable fats with polyunsaturated fatty acids omega-3 using fish oil

Polyunsaturated fatty acids of the omega-3 series, especially very long chain – eicosapenta- and docosahexaenoic acid (EPA, DHA) – exert a strongly desirable influence on health. However, their intake with the western-style diet is usually too low which favours development of many diseases (CVD, cancers, allergies, etc.). Nowadays elevation of EPA and DHA intake is commonly recommended, but almost the only dietary source of them is seafoods, especially fish. A new way to increase the intake of long-chain omega-3 without radical changes of eating patterns is enrichment of regularly consumed foods with unhydrogenated fish oil. The aim of this study was to establish sensory and nutritionally acceptable enrichment level of low-calorie spreadable fats (soft margarine and mix of butter and vegetable oil) with EPA and DHA by addition of fish oil preparations (ROPUFA – 30% EPA, DHA and MARITEX – 10%), and evaluation of the stability of enriched spreads during storage (sensory and chemical). It was shown that tested spreadable fats might be enriched up to 1% EPA, DHA (i.e. 3% ROPUFA, 8% MARITEX), and that this had no significant influence on sensory acceptability. Both used fish oils which exerted similar influence on the quality of fats. An enriched mix of butter and vegetable oil and margarine may be stored up to 3 and 6 weeks respectively without significant decrease of quality. Peroxide value and acid numbers were not much affected by enrichment and storage. Daily portion (25–30 g/day) of spreadable fats enriched on the level established in the study may provide 0.2–0.3 g EPA, DHA, significantly increasing the amount of long-chain omega-3 in the diet above those eaten normally.     

Suppression of serum lipid transfer proteins involved in high-density lipoprotein cholesterol metabolism by intensive insulin therapy in the first year of type 1 diabetes mellitus: Prospective InLipoDiab1 study

Background and aimsCholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) are crucial proteins in reverse cholesterol transport. There are insufficient data on regulating these proteins by insulin therapy in type 1 diabetes mellitus (T1DM). We aimed to assess prospectively the impact of insulin therapy initiation on transfer proteins serum levels in adults with newly diagnosed T1DM.Methods and results57 adults with newly diagnosed T1DM were enrolled in the InLipoDiab1 Study. All participants were treated with subcutaneous insulin in the model of intensive insulin therapy since the diagnosis of diabetes. Serum PLTP and CETP concentrations were measured at diagnosis, after three weeks, six months, and after one year of insulin treatment, using the immunoenzymatic method ELISA.A significant decrease in PLTP and CETP concentrations were demonstrated during twelve months of insulin therapy in newly diagnosed T1DM. The dynamics of changes in the level of these proteins varied depending on the occurrence of remission after a year of the disease. In the group without remission, a significant decrease in PLTP and CETP levels appeared after six months of follow-up. The remission group was characterized by a decrease in proteins concentration only after one year of treatment. In the non-remission group, significant negative correlations were found between the daily dose of insulin and levels of PLTP and CETP.ConclusionExogenous insulin is an inhibitor of lipid transfer proteins involved in high-density lipoprotein cholesterol metabolism in the first year of treatment.