Volume 26, Issue 2

It has been documented that telomere-associated cellular senescence may contribute to certain age-related disorders, and telomere length (TL) may be an informative biomarker of healthy aging. Hormone-brain-aging behavior-modulated telomere dynamics and changes in telomerase activity are consistent elements of cellular alterations associated with changes in proliferative state, and these processes are consequently considered as the new therapeutic drug targets for physiological control with advanced drug delivery and nutritional formulations. We raise and support a therapeutic concept of using nonhydrolyzed forms of naturally occurring neuron-specific imidazole dipeptide-based compounds carnosine and carcinine, making it clinically possible that slowing down the rate of telomere shortening could slow down the human aging process in specific tissues where proliferative senescence is known to occur, with the demonstrated evidence of telomere shortening that appeared to be a hallmark of oxidative stress and disease. Carnosine released from skeletal muscle during exercise may be transported into the hypothalamic tuberomammillary nucleus (TMN) histamine neurons and hydrolyzed. The resulting L-histidine may subsequently be converted into histamine, which could be responsible for the effects of carnosine on neurotransmission and hormone-like antiaging physiological function. The preliminary longitudinal studies of elderly individuals suggest that longer telomeres are associated with better survival, and an advanced oral nutritional support with nonhydrolyzed carnosine (or carcinine and patented compositions thereof) is a useful therapeutic tool for a critical TL maintenance that may fundamentally be applied in the treatment of age-related sight-threatening eye disorders, prolonged life expectancy, increased survival and chronological age of an organism in health control, smoking behavior, and disease.   “Our pleasures were simple—they included survival.”    —Dwight D. Eisenhower, 34th President of the United States, 1953–1961

Background: Investigation of the direct link between l -carnitine (LC), a quaternary ammonium compound that facilitates the passage of unsaturated fatty acids into the mitochondrial matrix, and free calcium (Ca 2+ ) is needed to explain a number of varying results obtained from different in vitro and in vivo studies of LC as a supplement. Methods: The chemical structure of LC, which contains oxygen ligand atoms, prompted to measure its activity as a Ca 2+ chelator. The measurement was carried out spectrophotometrically by measuring the reduction in the formation of Ca 2+ - o -cresolphthalein complexone (Ca-CPC) in the presence of different doses of LC (0.075, 0.75, and 7.5 mM) compared to the control (0.0 mM LC). Results: The effect of LC was measured as a free entity in solution and when added to human serum. Our results showed a significant decrease (p<0.05) in the average absorbance of Ca-CPC in the presence of LC compared to the control. Conclusions: In conclusion, LC exhibits a significant Ca 2+ chelating activity. As Ca 2+ is vital in the biochemical and physiological processes of living cells, LC could be affecting the calcium-dependent biological systems by limiting the levels of free Ca 2+ . Examples include decelerating the blood clotting process, amplifying the effect of anticoagulants, reducing nitric oxide synthase activity, inhibiting platelet aggregation, and decreasing sperm motility.

Background: We are constantly affected by changes in space weather. The principal “players” are solar activity (SA), geomagnetic activity (GMA) and antagonistic to them, cosmic ray activity (CRA) and high energy proton flux. CRA is measured by neutron activity on the earth’s surface in imp/min. SA and GMA are linked and serve as a shield for the earth from CRA. For a long time SA and GMA were the main areas of studies. The aim of this study was to compare some effects of the mentioned forces and discuss the temporal distribution of both groups of space weather, in relation to their effects on humans. Methods: The time distribution of GMA storms (daily) was compared with quiet (low) GMA, with higher CRA (neutron activity). Space weather data were obtained from the USA, Russia and Finland. Results: A total of 4383 days were analyzed in the years 2000–2012. A total of 71 days (1.62%) of geomagnetic storms (GS) and 2753 days (63.8%) of quiet (I 0 ) GMA were registered. A second study was provided including the years 1983–2007 (9131 days); here 3800 days (41.62%) were quiet GMA days and 400 storm days (4.38%). According to publications in the medical literature, many phenomena are connected with the extremes of space weather. Conclusions: Despite a great number of publications and the significant role of GS, it is a relatively rare event and most medical emergencies and deaths occur on days of low GMA, accompanied by higher CRA (neutron activity). High neutron activity deserves more attention when analyzing space effects on human health and their mechanism of action.

Background: Our present study was carried out to explore the potential role of the methanol extract from the leaves of Phlogocanthus thyrsiflorus (PT) Nees. in central and peripheral analgesic activities using hot plate and acetic acid-induced writhing methods. We also tested the anti-inflammatory effects and anti-oxidant activity using carrageenan-induced paw edema and the DPPH method, respectively. Methods: Methanol extracts of PT leaves were prepared using 500 g powder in 1.8 L methanol by percolation method, followed by evaporation in a rotary evaporator under controlled temperature and pressure. The crude methanol extract was dried by freeze drier and preserved at 4 °C. Results: Oral administration of PT significantly (p<0.05) increased the reaction time at 55.73% (250 mg/kg) and 72.81% (500 mg/kg) inhibition (p<0.05) in the hot plate test at 3 h. PT significantly (p<0.05) inhibited 42.17% (250 mg/kg) and 56.63% (500 mg/kg) acetic acid-induced writhing. PT leaves (250 and 500 mg/kg) also significantly (p<0.05) inhibited paw edema 6 h after carrageenan injection. Furthermore, this plant showed significant (p<0.05) free radical-scavenging activity at a dose range of 25–800 μg/mL. Conclusions: Based on the findings, we can conclude that PT leaf possesses analgesic, anti-inflammatory, and anti-oxidant activities. Preliminary phytochemical study of PT leaves revealed the presence of flavonoids, tannins and triterpens in methanol extract which could be correlated with its observed biological activities.

Background: The use of vascular endothelial growth factor (VEGF) inhibitors may cause fetal harm and systemic side effects in the mother, so these drugs are contraindicated in pregnancy. We report a case of inadvertent administration of two intravitreal bevacizumab injections in a woman with diabetes mellitus type 1, 5 days before ovulation (±3 days) and during the 5th gestational week, respectively. The patient had a past history of both miscarriage and requirement for cesarean section for preeclampsia. Methods: Observational case report. Results: The patient did not have any drug-related adverse event and delivered a healthy full-term infant, reaching all developmental milestones appropriately during infancy. Conclusions: Intravitreal drug injections did not result in any detectable adverse event in the mother and infant although she had a significant past obstetric history. However, there have been no studies evaluating the effects of bevacizumab in pregnant women and suggesting that intravitreal drug injection in this patient is safe. Until more is known about this, it seems reasonable to avoid treatment with this drug a few weeks before and during pregnancy.

Background: Chlorogenic acid is a major phenolic compound that forms a substantial part of plant foods and is an ester of caffeic acid and quinic acid. However, the effect of the structures of both chlorogenic and caffeic acids on their antioxidant and antidiabetic potentials have not been fully understood. Thus, this study sought to investigate and compare the interaction of caffeic acid and chlorogenic acid with α-amylase and α-glucosidase (key enzymes linked to type 2 diabetes) activities in vitro. Methods: The inhibitory effect of the phenolic acids on α-amylase and α-glucosidase activities was evaluated. Thereafter, their antioxidant activities as typified by their 1,1-diphenyl-2 picrylhydrazyl radical scavenging ability and ferric reducing antioxidant properties were determined. Results: The results revealed that both phenolic acids inhibited α-amylase and α-glucosidase activities in a dose-dependent manner (2–8 μg/mL). However, caffeic acid had a significantly (p<0.05) higher inhibitory effect on α-amylase [IC 50 (concentration of sample causing 50% enzyme inhibition)=3.68 μg/mL] and α-glucosidase (IC 50 =4.98 μg/mL) activities than chlorogenic acid (α-amylase IC 50 =9.10 μg/mL and α-glucosidase IC 50 =9.24 μg/mL). Furthermore, both phenolic acids exhibited high antioxidant properties, with caffeic acid showing higher effects. Conclusions: The esterification of caffeic acid with quinic acid, producing chlorogenic acid, reduces their ability to inhibit α-amylase and α-glucosidase activities. Thus, the inhibition of α-amylase and α-glucosidase activities by the phenolic acids could be part of the possible mechanism by which the phenolic acids exert their antidiabetic effects.

Background: Heparinised blood was exposed to osmotic lysis in hypotonic buffered saline to evaluate erythrocyte membrane stability. When K 3 EDTA blood was used, it added more to the ionic content of blood than heparin. The influence of suspending media’s ionic strength on the osmotic stability of Sahel goat erythrocytes was investigated by replacing the ionic saline with non-ionic saccharide (sucrose or glucose) and assessing the effect of using EDTA blood instead of heparinised blood. Results: The erythrocyte osmotic fragility curve in saline was hyperbolic even when the ionic concentration was reduced by 50% with saccharides. Haemolysis was higher with EDTA than heparinised blood at saline concentrations of 90 and 150–180 mosmol/L. The fragility curve was sigmoidal and shifted to the left when saline was completely substituted with a saccharide. The non-ionic saccharides increased erythrocyte osmotic resistance linearly (r=0.88; p<0.02) from median to minimal hyposmolarities (150–300 mosmol/L) and reduced the osmolyte concentration at median fragility by 36%. No effect occurred at <30–120 mosmol/L and >90% fragility; and saccharide concentrations were almost non-lytic at comparable saline concentrations evoking <10% haemolysis. Fragilities were neither affected by period (30–60 min) of incubation nor the type of saccharide used. Conclusions: In this study, the variation in osmotic stability of caprine erythrocytes was linked to ionic strength of the suspending extracellular media which seemed to exert an influence through transmembrane ion fluxes and regulatory volume changes in erythrocytes.

Background: This study was carried out to evaluate the anti-inflammatory and the analgesic potentials of Acalypha wilkesiana leaf extract in experimental animals. Methods: The anti-inflammatory potential was investigated using an acute rat model. Aspirin at 150 mg/kg, indomethacin at 10 mg/kg as positive control, and methanolic extracts and solvent fractions of A. wilkesiana at doses of 400 and 200 mg/kg, respectively, were administered orally to rats and compared with a negative control group given 10 mL/kg Tween 80. At an A. wilkesiana dose of 400 mg/kg body weight, the analgesic effect was also studied using the hot plate method and the acetic acid-induced writhing model in mice. Results: Percentage inhibition of the paw volume was highest in rats administered indomethacin (85.7%) followed by the group administered methanolic extract of A. wilkesiana (74.1%), whereas the group given aspirin had 65.5% inhibition of edema and the group given a 200 mg/kg dose of chloroform fraction of A. wilkesiana had 93% inhibition of increase in paw volume, a value higher than the performance of the standard drugs indomethacin (85%) and aspirin (68%). Also, the extract caused an increase in the reaction time in the hot plate test and in the acetic acid test. The mean number of writhings was significantly reduced in the group of mice administered 400 mg/kg extract of A. wilkesiana leaves (25.8±1.3) when compared with the control (46.7±1.4) but higher than the group of mice administered the standard analgesic agent paracetamol (23.5±1.3). Conclusions: This study suggested that A. wilkesiana leaves have anti-inflammatory and analgesic potential comparable with those of standard drugs.

Background: Colon cancer is one of the most common cancers in both men and women. The present study is an effort to unravel the anticarcinogenic effects of rosmarinic acid (RA) in 1,2-dimethylhydrazine (DMH)-induced rat colon carcinogenesis. Administration of DMH induces multiple tumors in the rat colon, which mimics human colon cancer. Methods: Male Wistar rats were divided into six groups and fed a high-fat diet. Group 1 served as control, group 2 rats were given RA [5 mg/kg body weight (b.w.)] orally every day for a total period of 30 weeks, and groups 3–6 were given weekly injections of DMH (20 mg/kg b.w. subcutaneous) once a week in the groin for the first 15 weeks. In addition to DMH, groups 4–6 received RA at a dose of 5 mg/kg b.w. during the initiation and postinitiation stages, and also throughout the entire study period. Colon tissues were examined histologically; further, the extent of oxidative stress was assessed by measuring lipid peroxidation and antioxidant levels in the colonic mucosa of rats. Results: Macroscopic and microscopic tumors were identified in all the groups that received DMH. The results revealed that supplementation with RA significantly inhibited the tumor formation and tumor multiplicity in DMH-treated rats. RA supplementation to DMH-administered rats significantly reduced the cell proliferation markers, namely, argyrophilic nucleolar organizing regions as well as proliferative cell nuclear antigen labeling index. In addition, RA supplementation reduces the expressions of tumor necrosis factor-α, interlukin-6, and cyclooxygenase-2, and modulates the expression of p65. Conclusions: The above findings clearly underline the chemopreventive efficacy of RA against DMH-induced colon carcinogenesis.

Background: The goal of this study was to evaluate the cerebroprotective and cognition-enhancing activities of the aqueous Vitex trifolia ( Vt ) L. (Verbenaceae) leaf extract against scopolamine-induced amnesia and in normal rats. Methods: Reference or working memory and long-term memory in rodents were tested by experimental paradigms like passive avoidance (PA) and T-maze (TM), respectively. TM and Morris water maze (MWM) were used to screen putative spatial or localization task and the navigation memory-enhancing activities of Vt extract, respectively. In both the PA and TM models, scopolamine (0.5 mg/kg, intraperitoneal, 30 min prior to the trial) was used to induce amnesia, and donepezil (3 mg/kg/day for 15 days) was used as a standard antiamnesic drug. In MWM, two doses of Vt extract were tested against normal control rats. The aqueous Vt extract was prepared as a suspension in 0.5% carboxymethyl cellulose and administered orally at two doses (10 and 20 mg/kg/day) for 15 days to the respective group of rats. Results: The higher dose (20 mg/kg) of plant extract exhibited significant (p<0.01) antiamnesic activity in the PA and TM models vs. the control. In the MWM test, at probe trial, Vt extract 20 mg/kg showed the least escape latency time, which was statistically significant (p<0.01) and exhibited maximum percentage of time spent in the probe quadrant by 60.75%. Conclusions: These results partly substantiate the traditional use of Vt leaves for improvement of cognition, indicating that daily administration of Vt leaves differentially could modulate short- and long-term learning and memory in rats probably through its battery of anticholinesterase, procholinergic, anti-inflammatory, antioxidant, and neuroprotective activities.

Background : The effect of Tridax procumbens aqueous ethanolic extract on the rat corpus cavernosum smooth muscles was evaluated in the present study. Method: Corpus cavernosum strips obtained from healthy, young, adult male Wistar albino rats (250–300 g) were precontracted with phenylephrine (10 –7 M) or KCl (60 mM) and then treated with various concentrations of T. procumbens extract (0.15–1.05 mg/mL). The change in corpus cavernosum strip tension was recorded. The interactions between T. procumbens extract with acetylcholine and with sodium nitroprusside were also evaluated. Results: The results indicated that corpus cavernosum strips relaxation induced by T . procumbens extract was concentration-dependent and this was significant (p<0.5). Pre-treatment with a nitric oxide synthase (NOS) inhibitor (N (1) nitro-L-arginine-methyl ester, l-NAME), did not completely inhibit the relaxation. However, T. procumbens extract (0.6 mg/mL) significantly (p<0.5) enhanced both acetylcholine- and sodium nitroprusside-induced corpus cavernosum strips relaxation. Conclusions: Results suggest that T. procumbens extract has a concentration-dependent relaxant effect on the isolated rat corpus cavernosum. The mechanism of action of T. procumbens extract is complex. A part of its relaxing effect is mediated directly by the release of NO from endothelium which may improve erectile dysfunction.