Cytotoxicity of oxidised lipids in cultured colonal human intestinal cancer cells (caco-2 cells)

In this study, we investigated the extent of the cytotoxicity effect of oxidised lipids and whether tea catechins namely (-)epigallocatechin-3 gallate (EGCG) decreased lipid peroxidation in caco-2 cells. Cells treated with 0-100mug/ml fish oil or methyl linoleate (ML) oxidised by UV irradiation for 24h, 48h and 72h, indicated a substantial decrease in cell viability especially in samples treated with 100mug/ml oxidised lipid. Addition of malondialdehyde (MDA) and hydroxynonenal (50muM) also reduced cell viability. Using EGCG (50muM) increased the viability of cells treated with 24h oxidised mackerel oil (72% live and 28% dead) compared with 48h oxidised mackerel oil (89% live and 11% dead) and 72h oxidised mackerel oil (71% live and 29% dead) as monitored by the MTT assay. Apoptosis of caco-2 cells by oxidised fish oil and ML and protection by EGCG was confirmed using fluorescence microscopy and caspase-3 presence by Western blotting.     

Rapidly released allergens from short ragweed pollen: II. Identification and partial purification

We have identified several basic allergens in 16-min extracts of short ragweed (Ambrosia elatior) pollen and obtained a partially purified fraction (G50 II) using a combination of ion-exchange (CM-Sephadex C25) and gel-filtration (Biogel P30 and Sephadex G50) procedures. G50 II was allergenically and antigenically distinct from known allergens antigen E, Ra3, and Ra5. It gave a highly symmetrical peak on Sephadex G50 (fine), corresponding to a molecular weight of 11,500 daltons, and a single band on SDS polyacrylamide gel electrophoresis under both reducing and nonreducing conditions. However, two cathodic antigens were detectable by both agarose electrophoresis and crossed immunoelectrophoresis. Allergenic activity of G50 II, assessed by puncture testing in ragweed-sensitive subjects, showed a characteristic pattern of response independent of patient response to AgE, Ra3, and Ra5. The major antigenic and allergenic component of G50 II is designated Ra6.     

Monogenic lupus due to DNASE1L3 deficiency in a pediatric patient with urticarial rash,hypocomplementemia, pulmonary hemorrhage,and immune-complex glomerulonephritis

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease and usually involves the skin, musculoskeletal system, and kidneys. More than 30 genes have been to monogenic lupus, so far. Monogenic lupus is often characterized by an early-onset, similar family history, and syndromic appearance. Herein we present a pediatric patient with DNASE1L3 deficiency, suffering from both urticarial skin lesions, recurrent hemoptysis, and renal involvement, eventually diagnosed as this rare monogenic lupus.The patient suffered from recurrent urticarial rash and hemoptysis since the age of 15 months of age. He had microscopic hematuria, mild proteinuria, hypocomplementemia, and positive antinuclear antibody, anti-dsDNA, and antineutrophil cytoplasmic antibodies. Renal biopsy yielded immunocomplex glomerulonephritis. Due to early-onset, similar sibling history and consanguineous parents, we suspected monogenic lupus and performed whole-exome sequencing, which further revealed a homozygous T97Ifs*2 mutation (NM_004944.4: c.290_291delCA/p.Thr97Ilefs*2) in DNASE1L3 gene.In conclusion, DNASE1L3 deficiency should be thought when juvenile SLE occurs with early disease-onset, pulmonary hemorrhage, glomerulonephritis, and recurrent urticarial rash along with ANCA positivity.     

Drive-thru pharmacy services: A way forward to combat COVID-19 pandemic

Countries around the globe have responded to pandemic preparedness and developed strategies to cope with the COVID-19 crisis. In this context, the role of healthcare professionals is of paramount importance. Pharmacists are playing a vital role in dealing, preparedness, prevention, protection, promoting access to medicines and to improve health outcomes during this crisis. In this context, “Drive-thru” pharmacy services improve access to medicines while ensuring the preventive measures suggested by the World Health Organization. This commentary provides an overview of opportunities and challenges related to the implementation of “drive-thru pharmacy services” and their role in improving public health during this crisis.     

Pharmacological treatment options for severe hypertriglyceridemia and familial chylomicronemia syndrome

Introduction: A spectrum of disorders, ranging from rare severe cases of homozygous null lipoprotein lipase deficiency (LPLD)–familial chylomicronemia syndrome (FCS) to heterozygous missense LPLD or polygenic causes, result in hypertriglyceridemia and pancreatitis. The effects of mutations are exacerbated by environmental factors such as diet, pregnancy, and insulin resistance.

Areas covered: In this review, authors discuss chronic treatment of FCS by ultra-low fat diets allied with the use of fibrates, omega-3 fatty acids, niacin, statins, and insulin-sensitizing therapies depending on the extent of residual lipoprotein lipase (LPL) activity; novel therapies in development target triglyceride (TG)-rich lipoprotein particle clearance. Previously, a gene therapy approach to LPL-alipogene tiparvovec showed that direct targeting of LPL function reduced pancreatitis events. An antisense oligonucleotide to apolipoprotein-C3, volanesorsen has been shown to decrease TGs by 70–80% and possibly to reduce rates of pancreatitis admissions. Studies are underway to validate its long-term efficacy and safety. Other approaches investigating the role of LPL modulating proteins such as angiopoietin-like petide-3 (ANGPTL3) are under consideration.

Expert opinion: Current therapeutic options are not sufficient for management of many cases of FCS. The availability of antisense anti-apoC3 therapies and, in the future, ANGPTL3 therapies may remedy this.     

Prevalence of peripheral arterial disease in patients with diabetes mellitus in a primary care setting

The aims of the study were to determine the prevalence of peripheral arterial disease (PAD) in diabetic patients and in different ethnic groups at a primary care setting, and to evaluate risk factors associated with PAD in these diabetic patients. A cross sectional study of 200 diabetic patients over 18 years old who attended a primary care clinic at a teaching hospital in Kuala Lumpur, Malaysia was carried out. Face-to-face interviews were conducted using structured questionnaires for demographic characteristics and risk factors evaluation. Blood pressure measurements, assessment of peripheral neuropathy and ankle brachial pressures were performed. PAD was diagnosed by an ankle brachial pressure index (ABPI) of <0.9 on either leg. The overall prevalence of PAD was 16% in this diabetic population. The prevalence of PAD was 5.8% in Malays, 19.4% in Chinese and 19.8% in Indians. The prevalence of peripheral neuropathy was 41%, foot ulcer 9.5%, and gangrene 3.0%. The presence of foot ulcer was weakly associated with PAD (P=0.052). No significant relationships were found between age, gender, smoking status, duration of diabetes mellitus, hypertension, dyslipidaemia, and PAD. PAD is common in the diabetic population of this study.     

Genotoxic assessment of oxcarbazepine and carbamazepine in drosophila wing spot test

In this study, different concentrations of two antiepileptic drugs, carbamazepine (CBZ) and oxcarbazepine (OXC), have been evaluated for genotoxicity in the wing spot test of Drosophila melanogaster. The wing spot test detects different kinds of somatic mutations and allows detection of mitotic recombinations. Third-instar larvae trans-heterozygous for two genetic markers mwh and flr, were treated at different concentrations of the drugs. Oxcarbazepine exposure concentrations were 1.88, 3.75, 7.50 and 15mug/ml. Carbamazepine exposure concentrations were 5, 10, 20 and 40mug/ml. In addition, the observed mutations were classified according to size and type of mutation per wing. CBZ was genotoxic in terms of total mutations per wing in the highest two doses; the same was true for OXC in the highest three doses. Survival rates of flies used in the experiments were significantly lower than that of the control group showing both drugs to have toxic effects to Drosophila melanogaster larvae. Clone formation frequency for 10(5) cells was lower in OXC than CBZ. However this was lower than the critical genotoxicity frequency of 2.0.     

Chemotherapy in gallbladder carcinoma

Gallbladder cancer is an aggressive tumor. Its incidence varies according to geography. Surgery is the standard treatment for localized stage but there is no standard treatment in metastatic or locally advanced disease. Because of the rarity of bile tract cancer (BTC) and gallblader carcinoma (GBC), most studies have grouped all BTC and GBC together, and there are very few GBC-specific studies. In addition, there is a paucity of randomized controlled studies in this disease with small numbers of patients and inclusion bias. One randomized trial ABC-02?was well conducted and showed a survival benefit in favor of gemcitabine (GEM)+cisplatin (CDDP), which can be regarded as the standard in locally advanced BTC. Adjuvant therapy after surgical resection is not validated. Understanding the molecular mechanisms of carcinogenesis of GBC has opened the way for the use of targeted therapies. This new treatment would improve survival and quality of life of our patients.