New nanodrug design for cancer therapy: Its synthesis,formulation, in vitro and in silico evaluations

The aim of this study was to develop a novel nanosize drug candidate for cancer therapy. For this purpose, (S)-methyl 2-[(7-hydroxy-2-oxo-4-phenyl-2H-chromen-8-yl)methyleneamino]-3-(1H-indol-3-yl)propanoate (ND3) was synthesized by the condensation reaction of 8-formyl-7-hydroxy-4-phenylcoumarin with l -tryptophan methyl ester. Its controlled release formulation was prepared and characterized by different spectroscopic and imaging methods. The cytotoxic effects of ND3 and its controlled release formulation were evaluated against MCF-7 and A549 cancer cell lines, and it was found that both of them have a toxic effect on cancer cells. For drug design and process development, the molecular docking analysis technique helps to clarify the effects of some DNA-targeted anticancer drugs to determine the interaction mechanisms of these drugs on DNA in a shorter time and at a lower cost. By using the molecular docking analysis and DNA binding assays, the interaction between the synthesized compound and DNA was elucidated and non-binding interactions were also determined. To predict the pharmacokinetics, and thereby accelerate drug discovery, the absorption, distribution, metabolism, excretion and toxicity values of the synthesized compound were determined by in silico methods.     

Community-acquired hyperkalemia in elderly patients: risk factors and clinical outcomes

Background: Although the risk and related factors of hyperkalemia developed in the hospital are known in elderly, risk and related factors of community-acquired hyperkalemia (CAH) in this population are not well known. This study was performed to investigate the risk of CAH in elderly and evaluate the related factors and clinical outcomes.

Study design, setting and participants, intervention: Patients (aged ≥65 years) with hyperkalemia were screened. Group 1 (young-old); 65–74 years/old, Group 2 (middle-old); 75–84 years/old, Group 3 (oldest-old); ≥85 years/old, and Group 4 (control group); ≥65 years/old (normal serum potassium levels). The relation between CAH and hospital expenses (HE), the number of comorbid diseases (NCD), and all-cause of mortality rates (MR) were evaluated. We also investigated whether drugs, sex, and NCD are risk factors for the development of CAH.

Results: There was a positive correlation between serum potassium levels and length of hospital stay, MR, HE, and NCD (p?<?0.001). Risk factors for CAH were the use of non-steroidal-anti inflammatory drugs (NSAIDs) (Odds Ratio [OR]: 2.679), spironolactone (OR: 2.530), and angiotensin converting enzyme inhibitors (ACEI) (OR: 2.242), angiotensin receptor blockers (ARB) (OR: 2.679), ≥2 comorbid diseases (OR: 2.221), female gender (OR: 2.112), and renal injury (OR: 5.55). CAH risk was found to be increased 30.03 times when any of ACEI, ARB, NSAIDs, or spironolactone is given to a patient with a renal injury.

Conclusion: Use of NSAIDs, ACEI, ARB, spironolactone and increased NCD are all independent risk factors for CAH in the elderly, especially in patients with kidney diseases.     

How Mentor Support Interacts With Mother and Teacher Support in Predicting Youth Academic Adjustment: An Investigation Among Youth Exposed to Big Brothers Big Sisters of Canada Programs

This study examines three potential contributions (i.e., additive only, hierarchical compensatory, and hierarchical conditional) of mentor support to youth academic adjustment, taking into account interactions with support from mothers and teachers. We derived data from a larger study of the Big Brothers Big Sisters (BBBS) of Canada community mentoring program. The sample included 427 youth (average age 9.8 years; 64% girls, 56% White) who received one-to-one community-based mentoring for at least three months. We assessed perceptions of support from mothers and teachers before the match and assessed perceptions of support from mentors five times throughout the mentoring experience. Hierarchical linear regression analyses showed that mentor support predicted positive changes in youth academic adjustment (i.e., school attitude, academic self-efficacy, assistance seeking, and problem solving) mainly when mentees already reported high support from their mother. This finding clearly supports the conditional model and invites researchers to question the assumption that mentoring constitutes a corrective experience for young people (i.e., the compensatory model). BBBS agencies are strongly encouraged to involve parents in the mentoring process and to view them as experts, assets, and allies in their effort to meet the youth’s needs.     

Cytomegalovirus infection in patients with glomerular diseases treated with cyclophosphamide: a single-center prospective study

International Urology and Nephrology - Cytomegalovirus infection is an important complication in immunocompromised patients. As few studies have shown that cyclophosphamide treatment is a risk...     

Phytochemical constituents,biological activities,and health‐promoting effects of the genus Origanum

Origanum species are mostly distributed around the Mediterranean, Euro‐Siberian, and Iran‐Siberian regions. Since time immemorial, the genus has popularly been used in Southern Europe, as well as on the American continent as a spice now known all over the world under the name “oregano” or “pizza‐spice.” Origanum plants are also employed to prepare bitter tinctures, wines, vermouths, beer, and kvass. The major components of Origanum essential oil are various terpenes, phenols, phenolic acids, and flavonoids with predominant occurrence of carvacrol and thymol (with reasonable amounts of p‐cymen and ‐terpinene) or of terpinene‐4‐ol, linalool, and sabinene hydrate. Many species of Origanum genus are used to treat kidney, digestive, nervous, and respiratory disorders, spasms, sore throat, diabetes, lean menstruation, hypertension, cold, insomnia, toothache, headache, epilepsy, urinary tract infections, etc. Origanum essential oil showed potent bioactivities owing to its major constituents' carvacrol, thymol, and monoterpenes. Several preclinical studies evidenced its pharmacological potential as antiproliferative or anticancer, antidiabetic, antihyperlipidemic, anti‐obesity, renoprotective, antiinflammatory, vasoprotective, cardioprotective, antinociceptive, insecticidal, and hepatoprotective properties. Its nanotechnological applications as a promising pharmaceutical in order to enhance the solubility, physicochemical stability, and the accumulation rate of its essential oils have been investigated. However, Origanum has been reported causing angioedema, perioral dermatitis, allergic reaction, inhibition of platelet aggregation, hypoglycemia, and abortion. Conclusive evidences are still required for its clinical applications against human medical conditions. Toxicity analyses and risk assessment will aid to its safe and efficacious application. In addition, elaborate structure–activity studies are needed to explore the potential use of Origanum‐derived phytochemicals as promising drug candidates.     

Protective effect of rutin on mercuric chloride-induced reproductive damage in male rats

This study investigated the effects of rutin against reproductive damage caused by toxic mercury in male rats. Thirty-five Sprague Dawley rats were used. Control group was injected with saline for 7 days. The rutin-100 group received 100 mg/kg/b.w. rutin for 7 days. Mercuric chloride (HgCl₂) group received 1.23 mg/kg/b.w. of HgCl₂ for 7 days. Mercury chloride + rutin-50 group received 50 mg/kg/b.w. rutin and HgCl₂ 1.23 mg/kg/b.w. for 7 days. HgCl₂ + rutin-100 group received 100 mg/kg/b.w. rutin and HgCl₂ 1.23 mg/kg/b.w. for 7 days. It was detected that HgCl₂ treatment increased malondialdehyde (MDA) levels, tumour necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2) expressions, necrosis and degeneration of spermatogonium, dead and abnormal sperm percentages; tubular walls thinning; and decreased antioxidant enzyme activities and sperm motility. It was determined that rutin application reduced testicular damage caused by HgCl₂. In conclusion, rutin administration may treat HgCl₂ toxicity in testes.     

A newborn infant with generalized glutathione synthetase deficiency

Pyroglutamic aciduria (5-oxoprolinuria) is a rare autosomal recessive disorder caused by either glutathione synthetase deficiency (GSSD) or 5-oxoprolinase deficiency. The severe form of the disease, generalized GSSD, is characterized by acute metabolic acidosis, usually present in the neonatal period with hemolytic anemia and progressive encephalopathy. We report a female infant who had a severe metabolic acidosis with high anion gap, hemolytic anemia, and hyperbilirubinemia. High level of 5-oxoproline was detected in her urine and a diagnosis of generalized GSSD was made. She died of severe metabolic acidosis and sepsis at the age of six weeks.     

Serum insulin-like growth factor 1 and growth hormone levels of hypoxic-ischemic newborns

A number of growth factors, their binding proteins, and their receptors have been shown to be induced in the hypoxic-ischemic (HI) brain. In this prospective study, we aimed at determining the levels of insulin-like growth factor 1 (IGF-1), growth hormone (GH), and cortisol in HI babies and at identifying whether they differ from the levels of control infants. The serum IGF-1 levels were measured after the first 12-24 h of life, and the measurements were repeated on the 5th and 10th days of life for babies with HI encephalopathy (n = 18) and on the 10th day of life for controls (n = 19). Blood samples for measurement of cortisol and GH from both HI and control groups were collected after the first 12-24 h of life. There were 11 babies in the mild-to-moderate (stages I and II) group and 7 babies in the severe (stage III) group according to Sarnat and Sarnat. The IGF-1 levels of the HI group measured after 12-24 h [78.5 +/- 27.9 (range 9-123.4) ng/ml] and on the 10th day [72.2 +/- 36.8 (range 29.7-159.2) ng/ml] of life were statistically significantly lower than the IGF-1 levels of the control group [121.5 +/- 50.4 (range 74.4-280.5) ng/ml and 133.1 +/- 34.4 (range 65.9-202) ng/ml, respectively] (p = 0.002 and p = 0.001, respectively). But there was no statistically significant difference between mild-to-moderate HI group and severe HI group in terms of IGF-1 levels after 12-24 h and 5 and 10 days of life (p > 0.05). Also there was no statistically significant difference in IGF-1 values after the first 12-24 h and after 10 days of life between HI subjects who died or survived (p > 0.05). The GH levels of the HI group after the first 12-24 h of life [34.6 +/- 32.3 (range 0.1-120) mIU/l] were statistically significantly higher than those in the control group [10.4 +/- 4.5 (range 3.7-16.9) mIU/l] (p = 0.005). There was no statistically significant difference in the serum cortisol levels between HI and control groups after the first 12-24 h of life [18.7 +/- 17.0 (range 1.6-65.1) microg/dl vs. 10.8 +/- 5.4 (range 3.0-23.2) microg/dl] (p > 0.05). No statistically significant correlation was found between IGF-1 levels and GH and cortisol levels of the HI encephalopathy group [r = -0.113 (p > 0.05) and r = 0.108 (p > 0.05), respectively]. In conclusion, this study showed decreased levels of serum IGF-1 and increased levels of GH which may be secondary to serum IGF-1 influx from the circulation to the brain as a protective mechanism or may be due to some cytokines which alter the GH/IGF axis, inhibit the action of IGF-1, and stimulate IGF-binding protein 1.