Serum levels of leptin and adiponectin in patients with autoimmune Hashimoto's thyroiditis.

INTRODUCTION: Adipose tissue is immunologically and hormonally active, and these effects are mediated largely by adipocytokines. Thyroid hormones regulate metabolism and organ function, and Hashimoto's thyroiditis (HT) is the most common autoimmune disease affecting thyroid function. AIM: To evaluate the levels of the adipocytokines leptin and adiponectin in patients with autoimmune HT, and to perform a comparative intragroup analysis in patients with different stages of gland functional activity, and in a control group. MATERIALS AND METHODS: Ninety-five patients with HT and 21 healthy controls were enrolled in the study. Venous blood was taken without anticoagulants after at least 12 hours of fasting, and serum samples were frozen at -70°C until analysis. Serum levels of leptin and adiponectin were determined by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum levels of leptin in HT patients were higher than those in the control group (4.5±5.2 ng/mL vs. 1.9±1.3 ng/mL). The hypothyroid patient's group showed significantly higher levels of leptin than those of the healthy controls (5.1±5.2 ng/mL vs. 1.9±1.3 ng/mL), (p=0.031). Leptin levels correlated positively with body mass index (r=0.533, p.

Pre- and Post-Endurance Training Mitigates the Rat Pilocarpine-Induced Status Epilepticus and Epileptogenesis-Associated Deleterious Consequences.

Epilepsy is a brain disorder characterized by recurrent epileptic seizures and neurobiological, physiological, mood, and cognitive consequences. In the last decade, the beneficial effects of regular physical exercise have been investigated in patients with neurodegenerative diseases such as epilepsy. However, data on its beneficial effects and underlying mechanisms are still insufficient. The objective of the current study was to investigate the effects of endurance training, applied before and after pilocarpine (Pilo) administration, on status epilepticus (SE) severity, and its relation to epileptogenesis deleterious consequences during the chronic epileptic phase. Long-term aerobic training, applied four weeks before SE and eight weeks after SE, elevated the threshold to induce SE and reduced spontaneous motor seizures. The protective effect of this alternative approach on seizure susceptibility resulted in improved memory responses, and alleviated comorbid depression in epileptic rats. The exercised epileptic rats had improved markers of oxidative stress by decreasing lipid peroxidation and increasing the levels of glutathione and activity of superoxide dismutase in the rat hippocampus. Aerobic training managed to ameliorate the neuroinflammation by decreasing the levels of TNF-α and IL-1ß in the hippocampus. Our results suggest that regular physical training predisposes the subjects to crucial plastic changes, leading to increased resistance to SE and the development of epileptogenesis.

Oncometabolites in urine - a new opportunity for detection and prognosis of the clinical progress of verified prostate cancer-a pilot study.

BACKGROUND: Oncometabolites provide a new approach towards the diagnostics and prognosis of the clinical progress of prostate cancer (PCa). This study is about the diagnostic and predictive value of a panel of urinary oncometabolites (ethanolamine, kynurenine, ß-alanine, α-alanine, leucine, isoleucine, γ-aminobutyric acid, and sarcosine) and correlation with prostate-specific antigen (PSA) and Gleason score in patients diagnosed with prostate cancer. METHODS: The participants in this cross-sectional study were divided into PCa group (101 patients who matched the including criteria, average age 71) and control group (52 individuals, with no evidence of malignancy, without oncological and other chronic diseases, and without prostate gland pathology, average age 40). The criteria to be included in the PCa group were as follows: i) being diagnosed with prostate cancer, based on digital rectal examination (DRE), prostate ultrasound investigation, or biopsy; ii) not being subjected to a surgical or any other treatment; iii) not having any other concomitant oncological diseases, renal failure, diabetes mellitus. The urinary concentration of the selected metabolites was established through high-performance liquid chromatography with tandem mass spectrometry detection (HPLC-MS/MS). RESULTS: The comparison of both groups established a significantly different elevated concentration of ethanolamine, sarcosine and kynurenine, and a significantly different decreased concentration of ß-alanine and isoleucine in PCa group. No changes of the values were detected in the PCa group with PSA levels below and above 10 ng/mL and Gleason score below and above 6 (p > 0.05). To test whether combination of several variables is more powerful in discriminating between PCa and control group multiple logistic regression analysis was performed. A model including ethanolamine, sarcosine, kynurenine, ß-alanine, and isoleucine demonstrated negative predictive power (NPP) 76.2% and positive predictive power (PPP) 81.8%. DISCUSSION: Urinary concentrations of ethanolamine, sarcosine, kynurenine, ß-alanine, and isoleucine in PCa group differ significantly from that of control group. New expanded population studies are needed to discuss our results.

The anticonvulsant effect of chronic treatment with topiramate after pilocarpine-induced status epilepticus is accompanied by a suppression of comorbid behavioral impairments and robust neuroprotection in limbic regions in rats.

Epilepsy is a widespread neurological disorder frequently associated with a lot of comorbidities. The present study aimed to evaluate the effects of the antiseizure medication topiramate (TPM) on spontaneous motor seizures, the pathogenesis of comorbid mood and cognitive impairments, hippocampal neuronal loss, and oxidative stress and inflammation in a rat model of temporal lobe epilepsy (TLE). Vehicle/TPM treatment (80 mg/kg, p.o.) was administered 3 h after the pilocarpine (pilo)-induced status epilepticus (SE) and continued for up to 12 weeks in Wistar rats. The chronic TPM treatment caused side effects in naïve rats, including memory disturbance, anxiety, and depressive-like responses. However, the anticonvulsant effect of this drug, administered during epileptogenesis, was accompanied by beneficial activity against comorbid behavioral impairments. The drug treatment suppressed the SE-induced neuronal damage in limbic structures, including the dorsal (CA1 and CA2 subfield), the ventral (CA1, CA2 and CA3) hippocampus, the basolateral amygdala, and the piriform cortex, while was ineffective against the surge in the oxidative stress and inflammation. Our results suggest that neuroprotection is an essential mechanism of TPM against spontaneous generalized seizures and concomitant emotional and cognitive impairments.

Polyelectrolyte Multilayer Films as a Potential Buccal Platform for Drug Delivery.

The goal of this research was to study the potential of polyelectrolyte multilayers as buccal dosage forms for drug delivery and to investigate how the properties of the drugs impact the overall performance of the delivery system. Multilayer films based on the polyelectrolyte interaction between casein and chitosan were developed using benzydamine, tolfenamic acid and betahistine as model drugs. The samples were characterized for surface pH, moisture content and moisture absorption, swelling behavior and mucoadhesion. Additionally, surface morphology was investigated, as well as the drugs' physical state after incorporation in the multilayer films. The samples proved to be non-irritant (pH was within the physiological range), physically stable (moisture content and moisture absorption below 5%) and mucoadhesive, adsorbing from 60 to 70% mucin. The release behavior corelated to the swelling index profiles of the samples and was strongly dependent on the drug solubility. The developed multilayer films appeared to be an optimum delivery system for sparingly soluble drugs due to the high drug loading achieved.

Casein Microgels as Benzydamine Hydrochloride Carriers for Prolonged Release.

This research aims to investigate the properties of nano- and micro-sized casein hydrogels crosslinked by sodium tripolyphosphate as drug delivery systems. Benzydamine hydrochloride was chosen as a model hydrophilic drug. The gels were synthesized by varying different parameters: casein concentration, casein/crosslinking ratio, and addition of ethanol as a co-solvent. The electrostatic attractive interactions between the casein and the sodium tripolyphosphate were confirmed by FTIR spectroscopy. The particle sizes was determined by dynamic light scattering and varied in the range between several hundred nanometers and several microns. The yield of the gelation process was high for all investigated samples and varied between 55.3% and 78.3%. The encapsulation efficiency of the particles was strongly influenced by the casein concentration and casein/crosslinker ratio and its values were between 4.6% and 22.4%. The release study confirmed that casein particles are useful as benzydamine carriers and ensured prolonged release over 72 h.

Comparative Study on Microencapsulation of Lavender (Lavandula angustifolia Mill.) and Peppermint (Mentha piperita L.) Essential Oils via Spray-Drying Technique.

Essential oils have been studied for various applications, including for therapeutic purposes. There is extensive literature regarding their properties; however, their low stability limits their application. Generally, the microencapsulation of essential oils allows enhanced stability and enables the potential incorporation in solid dosage forms. Lavender and peppermint oils were encapsulated in microparticles using a spray-drying technique under optimized conditions: 170 °C temperature, 35 m3/h aspiration volume flow, and 7.5 mL/min feed flow. Arabic gum and maltodextrin were used as coating polymers individually in varying concentrations from 5 to 20% (w/v) and in combination. The microparticles were studied for morphology, particle size, oil content, and flowability. The formulated powder particles showed a high yield of 71 to 84%, mean diameter 2.41 to 5.99 µm, and total oil content of up to 10.80%. The results showed that both the wall material type and concentration, as well as the type of essential oil, significantly affected the encapsulation process and the final particle characteristics. Our study has demonstrated that the encapsulation of lavender and peppermint oils in Arabic gum/maltodextrin microparticles by spray-drying represents a feasible approach for the conversion of liquids into solids regarding their further use in powder technology.

Casein Micelles as Nanocarriers for Benzydamine Delivery.

The aim of the present work was to optimize the process parameters of the nano spray drying technique for the formulation of benzydamine-loaded casein nanoparticles and to investigate the effect of some process variables on the structural and morphological characteristics and release behavior. The obtained particles were characterized in terms of particle size and size distribution, surface morphology, production yield and encapsulation efficiency, drug-polymer compatibility, etc., using dynamic light scattering, scanning electron microscopy, differential scanning calorimetry, and Fourier transformed infrared spectroscopy. Production yields of the blank nanoparticles were significantly influenced by the concentration of both casein and the crosslinking agent. The formulated drug-loaded nanoparticles had an average particle size of 135.9 nm to 994.2 nm. Drug loading varied from 16.02% to 57.41% and the encapsulation efficiency was in the range 34.61% to 78.82%. Our study has demonstrated that all the investigated parameters depended greatly on the polymer/drug ratio and the drug release study confirmed the feasibility of the developed nanocarriers for prolonged delivery of benzydamine.

Effects of Lacosamide Treatment on Epileptogenesis, Neuronal Damage and Behavioral Comorbidities in a Rat Model of Temporal Lobe Epilepsy.

Clinically, temporal lobe epilepsy (TLE) is the most prevalent type of partial epilepsy and often accompanied by various comorbidities. The present study aimed to evaluate the effects of chronic treatment with the antiepileptic drug (AED) lacosamide (LCM) on spontaneous motor seizures (SMS), behavioral comorbidities, oxidative stress, neuroinflammation, and neuronal damage in a model of TLE. Vehicle/LCM treatment (30 mg/kg, p.o.) was administered 3 h after the pilocarpine-induced status epilepticus (SE) and continued for up to 12 weeks in Wistar rats. Our study showed that LCM attenuated the number of SMS and corrected comorbid to epilepsy impaired motor activity, anxiety, memory, and alleviated depressive-like responses measured in the elevated plus maze, object recognition test, radial arm maze test, and sucrose preference test, respectively. This AED suppressed oxidative stress through increased superoxide dismutase activity and glutathione levels, and alleviated catalase activity and lipid peroxidation in the hippocampus. Lacosamide treatment after SE mitigated the increased levels of IL-1ß and TNF-α in the hippocampus and exerted strong neuroprotection both in the dorsal and ventral hippocampus, basolateral amygdala, and partially in the piriform cortex. Our results suggest that the antioxidant, anti-inflammatory, and neuroprotective activity of LCM is an important prerequisite for its anticonvulsant and beneficial effects on SE-induced behavioral comorbidities.

Anticonvulsant Effects of Topiramate and Lacosamide on Pilocarpine-Induced Status Epilepticus in Rats: A Role of Reactive Oxygen Species and Inflammation.

BACKGROUND: Status epilepticus (SE) is a neurological disorder characterized by a prolonged epileptic activity followed by subsequent epileptogenic processes. The aim of the present study was to evaluate the early effects of topiramate (TPM) and lacosamide (LCM) treatment on oxidative stress and inflammatory damage in a model of pilocarpine-induced SE. METHODS: Male Wistar rats were randomly divided into six groups and the two antiepileptic drugs (AEDs), TPM (40 and 80 mg/kg, i.p.) and LCM (10 and 30 mg/kg, i.p.), were injected three times repeatedly after pilocarpine administration. Rats were sacrificed 24 h post-SE and several parameters of oxidative stress and inflammatory response have been explored in the hippocampus. RESULTS: The two drugs TPM and LCM, in both doses used, succeeded in attenuating the number of motor seizures compared to the SE-veh group 30 min after administration. Pilocarpine-induced SE decreased the superoxide dismutase (SOD) activity and reduced glutathione (GSH) levels while increasing the catalase (CAT) activity, malondialdehyde (MDA), and IL-1ß levels compared to the control group. Groups with SE did not affect the TNF-α levels. The treatment with a higher dose of 30 mg/kg LCM restored to control level the SOD activity in the SE group. The two AEDs, in both doses applied, also normalized the CAT activity and MDA levels to control values. In conclusion, we suggest that the antioxidant effect of TPM and LCM might contribute to their anticonvulsant effect against pilocarpine-induced SE, whereas their weak anti-inflammatory effect in the hippocampus is a consequence of reduced SE severity.

Aronia melanocarpa (Michx.) Elliot fruit juice reveals neuroprotective effect and improves cognitive and locomotor functions of aged rats.

The aim of the study was to investigate the effect of polyphenol-rich Aronia melanocarpa (Michx.) Elliot juice (AMJ) on learning ability and memory, and brain morphology of aged rats. A model of healthy male Wistar rats (24 months of age) divided in 2 groups was used: AMJ group supplemented orally with AMJ (10 mL/kg for 105 days) and old control (CO) group without supplementation. Activity cage test showed that AMJ supplemented rats increased the number of vertical movements compared with old controls (p < 0.05). In active avoidance test, supplemented rats increased the number of avoidances on 3rd, 4th and 5th days of learning session, compared with the respective day of old controls (p < 0.05). AMJ supplementation did not affect the mean neuronal number in the dentate gyrus but significantly increased the density of nerve fibers in the perforant path of the hippocampus (p < 0.05). AMJ supplementation increased acetylcholinesterase activity in hippocampus, which is a marker of improved functional activity of the cholinergic neurons. These results indicate that AMJ induced ameliorating changes in the ability of old rats to learn tasks and improved their locomotor functions. AMJ showed a neuroprotective effect by increasing the density of nerve fibers in the hippocampal perforant pathway.

Chemical cross-linking: A feasible approach to prolong doxylamine/pyridoxine release from spray-dried chitosan microspheres.

Spray-dried chitosan microparticles have been widely exploited as vehicles for mucosal drug delivery. Despite their advantages as pharmaceutical formulations, one of the major challenges is achieving sustained drug release, which would diminish toxicity and dosage frequency. The aim of this study was to formulate mucoadhesive glutaraldehyde cross-linked chitosan microparticles loaded with doxylamine succinate and pyridoxine hydrochloride as potential nasal drug delivery systems with sustained release. Microparticle models were formulated via spray-drying technique, using glutaraldehyde in different concentrations (0.1-1.0 mg/mL) as a cross-linking agent for chitosan. The obtained particles were with spherical shape, smooth surface and median diameter of 4 µm. The drug entrapment efficiency was high (80.47%-94.25%), indicating a tendency to decrease at higher glutaraldehyde concentrations. FTIR data demonstrated that there were no chemical interactions between glutaraldehyde and the drugs. The in vitro studies showed that the cross-linking process substantially limited particles swelling. The cross-linked particles exhibited sustained drug release characteristics at pH 6.8 over a period of 5 h with an initial burst-effect in the first 30 min. Drug release followed Korsmeyer-Peppas kinetics. Although a decrease of the particles mucoadhesive properties was observed after modification, all cross-linked formulations demonstrated high in vitro adsorption of mucin. The proposed models of mucoadhesive microsphere with sustained drug release are a perspective ground for further development of a novel delivery system for nasal administration of doxylamine and pyridoxine.

Formulation and performance evaluation of betahistine dihydrochloride microspheres as sustained release systems.

UNLABELLED: Betahistine dihydrochloride is a histamine-like drug widely used in relieving the symptoms associated with Ménière's syndrome. Pharmacokinetic studies of betahistine have demonstrated that it has a short plasma half-life of 3-4 hours. In such cases frequent administration of the drug is required in order to keep plasma concentration within the therapeutic range. However, this may lead to noncompliance and aggravate patients' comfort. An advanced approach for achieving sustained release of drugs is their incorporation in microparticulate carriers. AIM: To design a sustained release microsphere formulation of betahistine providing reduced dose frequency and lower risk of side effects occurrence. MATERIALS AND METHODS: Betahistine-loaded chitosan microspheres were obtained via W/O emulsion solvent evaporation technique and were characterized for particle size, drug loading and entrapment efficiency. Drug release into phosphate buffer saline pH 7.4 was performed and dissolution profiles of the formulations were obtained. To study the mechanism of drug release from the microspheres the dissolution data was fitted to various mathematic models. RESULTS: Betahistine-loaded microspheres were produced with a high drug loading and entrapment efficiency. The microcarriers were spherical in shape with mean particle size of 3.82 µm to 7.69 µm. Betahistine release studies from the microspheres showed similar and slightly increasing dissolution profiles. The drug release proceeded in a controlled manner following Fickian diffusion. CONCLUSION: The obtained results suggest that betahistine-loaded chitosan microspheres prepared by solvent evaporation method are capable of sustained release of drugs and therefore can be used as drug delivery systems in the treatment of Ménière's syndrome.

High-performance liquid chromatographic determination of unreacted monomers and other residues contained in dental composites.

HPLC method was developed for determination of bisphenol A diglycidyl methacrylate (bis-GMA), bisphenol A diglycidyl acrylate (bis-GA), bisphenol A dimethacrylate (bis-DMA), glycidylmethacrylate (GMA) and triethylenglycol dimethacrylate (TEGDMA). Separation was carried out on a reversed phase Omnisphere 5 C18 column with a gradient mobile phase of CH3CN/H2O. UV detection was set at 205 nm and 275 nm parallel. The limits of quantification were found. The method has been applied for quantification of unreacted monomers trapped in polymer network of fillings.