Search Results (13)

Objectives: Due to poor treatment adherence and lifestyle-based interventions, chronic hypertension is a dominant risk factor predisposing individuals to heart failure and malignant arrhythmias. We investigated the impact of the postnatal acclimation of hairless SHR to ambient temperature that is, for them, below thermoneutrality, on the electrical coupling protein connexin-43 (Cx43) and pro-fibrotic markers in both heart ventricles of male and female hairless SHR rats compared to the wild SHR. Methods: Some 6-month-acclimated male and female hairless SHR as well as age- and sex-matched wild SHR were included and compared with the non-hypertensive Wistar strain. The left and right heart ventricles were examined for Cx43 topology, myocardial structure, and the histochemistry of capillaries. The protein levels of Cx43, relevant protein kinases, and extracellular matrix proteins (ECMs) were determined by immunoblotting. MMP-2 activity was assessed via zymography, and susceptibility to malignant arrhythmias was tested ex vivo. Results: Cx43 and its phosphorylated variant pCx43³⁶⁸ were significantly reduced in the left heart ventricles of wild SHR males, while to a lesser extent in the hairless SHR. In contrast, these proteins were not significantly altered in the right heart ventricles of males or in both heart ventricles in females, regardless of the rat strain. Pro-arrhythmic Cx43 topology was detected in the left heart ventricle of wild SHR and to a lesser extent in hairless SHR males. TGFβ protein was significantly increased only in the left ventricle of the wild SHR males. MMP-2 activity was increased in the right ventricle but not in the left ventricles of both males and females, regardless of the rat strain. Conclusions: The findings indicate that the postnatal acclimation of hairless SHR to ambient temperature hampers the downregulation of Cx43 in the left heart ventricle compared to wild SHR males. The decline of Cx43 was much less pronounced in females and not observed in the right heart ventricles, regardless of the rat strain. It may impact the susceptibility of the heart to malignant arrhythmias. Full article

Recently, the number of people acquiring tattoos has increased, with tattoos gaining significant popularity in people between 20 and 40 years old. Inflammation is a common reaction associated with tattooing. The purpose of this study was to evaluate a nanostructured lipid carrier loading pranoprofen (PRA-NLC) as a tattoo aftercare formulation to reduce the inflammation associated with tattooing. In this context, the in vitro drug release and the ex vivo permeation-through-human-skin tests using Franz cells were appraised. The tolerance of our formulation on the skin was evaluated by studying the skin’s biomechanical properties. In addition, an in vivo anti-inflammatory study was conducted on mice skin to evaluate the efficacy of the formulation applied topically after tattooing the animals. PRA-NLC showed a sustained release up to 72 h, and the amount of pranoprofen retained in the skin was found to be 33.48 µg/g/cm². The formulation proved to be well tolerated; it increased stratum corneum hydration, and no signs of skin irritation were observed. Furthermore, it was demonstrated to be non-cytotoxic since the cell viability was greater than 80%. Based on these results, we concluded that PRA-NLC represents a suitable drug delivery carrier for the transdermal delivery of pranoprofen to alleviate the local skin inflammation associated with tattooing. Full article

Pranoprofen (PRA)-loaded nanostructured lipid carriers (NLC) have been dispersed into blank gels composed of 1% of Carbomer 940 (PRA-NLC-Car) and 3% of Sepigel^® 305 (PRA-NLC-Sep) as a novel strategy to refine the biopharmaceutical profile of PRA, for dermal administration in the treatment of skin inflammation that may be caused by possible skin abrasion. This stratagem intends to improve the joining of PRA with the skin, improving its retention and anti-inflammatory effect. Gels were evaluated for various parameters such as pH, morphology, rheology, and swelling. In vitro drug release research and ex vivo permeation through the skin were carried out on Franz diffusion cells. Additionally, in vivo assays were carried out to evaluate the anti-inflammatory effect, and tolerance studies were performed in humans by evaluating the biomechanical properties. Results showed a rheological profile common of semi-solid pharmaceutical forms for dermal application, with sustained release up to 24 h. In vivo studies using PRA-NLC-Car and PRA-NLC-Sep in Mus musculus mice and hairless rats histologically demonstrated their efficacy in an inflammatory animal model study. No signs of skin irritation or modifications of the skin’s biophysical properties were identified and the gels were well tolerated. The results obtained from this investigation concluded that the developed semi-solid formulations represent a fitting drug delivery carrier for PRA’s transdermal delivery, enhancing its dermal retention and suggesting that they can be utilized as an interesting and effective topical treatment for local skin inflammation caused by a possible abrasion. Full article

This study developed a rapid manufacturing approach for a moisture sensor based on contactless jet printing technology. A compact measurement system with ultrathin and flexure sensor electrodes was fabricated. The proposed sensor system focuses on continuous urine measurement, which can provide timely information on subjects to ensure efficient diagnosis and treatment. The obtained results verify that the proposed sensor system can exhibit a typical responsivity of up to −7.76 mV/%RH in the high-sensitivity range of 50–80 %RH. A preliminary field experiment was conducted on a hairless rat, and the effectiveness of the proposed ultrathin moisture sensor was verified. This ultrathin sensor electrode can be fabricated in the micrometer range, and its application does not affect the comfort of the user. The ultrathin electrode sensors can be printed directly on the diaper or undergarment of the user for in situ urine health monitoring, particularly of infants and the elderly. Full article

The hearts of spontaneously hypertensive rats (SHR) are prone to malignant arrhythmias, mainly due to disorders of electrical coupling protein Cx43 and the extracellular matrix. Cold acclimation may induce cardio-protection, but the underlying mechanisms remain to be elucidated. We aimed to explore whether the adaptation of 9-month-old hairless SHR^M to cold impacts the fundamental cardiac pro-arrhythmia factors, as well as the response to the thyroid status. There were no significant differences in the registered biometric, redox and blood lipids parameters between hairless (SHR^M) and wild type SHR. Prominent findings revealed that myocardial Cx43 and its variant phosphorylated at serine 368 were increased, while an abnormal cardiomyocyte Cx43 distribution was attenuated in hairless SHR^M vs. wild type SHR males and females. Moreover, the level of β-catenin, ensuring mechanoelectrical coupling, was increased as well, while extracellular matrix collagen-1 and hydroxyproline were lower and the TGF-β1 and SMAD2/3 pathway was suppressed in hairless SHR^M males compared to the wild type strain. Of interest, the extracellular matrix remodeling was less pronounced in females of both hypertensive strains. There were no apparent differences in response to the hypothyroid or hyperthyroid status between SHR strains concerning the examined markers. Our findings imply that hairless SHR^M benefit from cold acclimation due to the attenuation of the hypertension-induced adverse downregulation of Cx43 and upregulation of extracellular matrix proteins. Full article

Interstitial fluid (ISF) bathes the cells and tissues and is in constant exchange with blood. As an exchange medium for waste, nutrients, exosomes, and signaling molecules, ISF is recognized as a plentiful source of biomolecules. Many basic and pre-clinical small animal studies could benefit from an inexpensive and efficient technique that allows for the in vivo extraction of ISF for the subsequent quantification of molecules in the interstitial space. We have previously reported on a minimally invasive technique for the extraction of ISF using a 3D-printed microneedle array (MA) platform for comprehensive biomedical applications. Previously, hairless animal models were utilized, and euthanasia was performed immediately following the procedure. Here, we demonstrate the technique in Sprague Dawley rats, without the need for hair removal, over multiple extractions and weeks. As an example of this technique, we report simultaneous quantification of the heavy metals Copper (Cu), Lead (Pb), Lithium (Li), and Nickel (Ni) within the ISF, compared with whole blood. These results demonstrate the MA technique applicability to a broader range of species and studies and the reuse of animals, leading to a reduction in number of animals needed to successfully complete ISF extraction experiments. Full article

Our goal was to prepare Span 60-based elastic nanovesicles (spanlastics (SPLs)) of tacrolimus (TCR) using the adapted ethanol injection method, characterize them, and evaluate their ability to improve the transdermal permeation of the active substance. The impact of two different concentrations of penetration enhancers, namely, propylene glycol and oleic acid, on the entrapment efficiency, vesicle size, and zeta potential was assessed. Moreover, in vitro release through a semipermeable membrane and ex vivo penetration through hairless rat skin were performed. Morphological examination and pharmacokinetics were performed for one selected formulation (F3OA1). TCR-loaded SPLs were effectively formulated with two different concentrations of permeation enhancers, and the effect of these enhancers on their physicochemical properties differed in accordance with the concentration and kind of enhancer used. The results of in vitro release displayed a considerable (p < 0.05) enhancement compared to the suspension of the pure drug, and there was a correlation between the in vitro and ex vivo results. The selected TCR-loaded nanovesicles incorporated into a gel base showed appreciable advantages over the oral drug suspension and the TCR-loaded gel. Additionally, the pharmacokinetic parameters were significantly (p < 0.05) improved based on our findings. Moreover, the AUC_0–7 ng·h/mL form F3 OA1 was 3.36-fold higher than that after the administration of the TCR oral suspension. Full article

The forkhead box N1 (Foxn1) transcription factor regulates biological processes of the thymus and skin. Loss-of-function mutations in Foxn1 cause the nude phenotype in humans, mice, and rats, which is characterized by hairless skin and a lack of thymus. This review focuses on the role of Foxn1 in skin biology, including epidermal, dermal, and dermal white adipose tissue (dWAT) skin components. In particular, the role of Foxn1 in the scar-forming skin wound healing process is discussed, underscoring that Foxn1 inactivity in nude mice is permissive for scar-less cutaneous wound resolution. Full article

Bioshell calcium oxide (BiSCaO) possesses deodorizing properties and broad microbicidal activity. This study aimed to investigate the application of BiSCaO ointment for the prevention and treatment of infection in chronic wounds in healing-impaired patients, without delaying wound healing. The bactericidal activities of 0.04, 0.2, 1, and 5 wt% BiSCaO ointment, 3 wt% povidone iodine ointment, and control (ointment only) were compared to evaluate the in vivo disinfection and healing of Pseudomonas aeruginosa-infected wounds in hairless rats. Treatment of the infected wounds with 0.2 wt% BiSCaO ointment daily for 3 days significantly enhanced wound healing and reduced the in vivo bacterial counts compared with povidone iodine ointment and control (no wound cleaning). Although 5 wt% BiSCaO ointment provided the lowest bacterial counts during 3 days’ treatment, it delayed wound healing. Histological examinations showed significantly advanced granulation tissue and capillary formation in wounds treated with 0.2 wt% BiSCaO ointment for 3 days compared to wounds treated with the other ointments. This study suggested that using 0.2 wt% BiSCaO ointment as a disinfectant for infected wounds and limiting disinfection to 3 days may be sufficient to avoid the negative effects of BiSCaO on wound repair. Full article

Transdermal delivery systems are emerging platforms for the delivery of donepezil hydrochloride (DH) for treating Alzheimer’s disease. The primary aim of this study was to develop polyvinyl alcohol and polyvinyl pyrrolidone blended hydrogels and to evaluate their feasibility for delivering DH via a transdermal route. Physicochemical properties, such as gel fraction (%), swelling ratio (%), weight loss (%), mechanical strength, elongation at break, and Young’s modulus of the prepared hydrogels were evaluated. Furthermore, in vitro skin permeation and in vivo pharmacokinetic studies were performed. With an increased concentration of propylene glycol (PG), the gel fraction (%), maximum strength, and elongation at break decreased. However, the swelling ratio (%) and weight loss (%) of hydrogels increased with increased PG content. The 26% PG-hydrogel was superior, with an enhancement ratio of 12.9 (*** p < 0.001). In addition, the 11% PG-hydrogel and 1% PG-hydrogel exhibited an enhancement ratio 6.30-fold (*** p < 0.001) and 2.85-fold (* p < 0.05) higher than that exhibited by control, respectively, indicating a promising effect of PG on skin permeation. In addition, in vivo pharmacokinetic studies on hairless rats assessed the expediency for transdermal delivery of DH. The transdermal delivery of optimized hydrogel-patches with two different doses of DH revealed that the maximum plasma concentration and area under the curve were dose dependent, and the time to reach the maximum concentration was 8 h. Thus, optimized hydrogels have the potential to enhance the transdermal delivery of DH and could be a novel clinical approach. Full article

Naked mole-rats are eusocial, hairless mammals that are uniquely adapted to their harsh, low-oxygen subsurface habitat. Although their encephalization quotient, a controversial marker of intelligence, is low, they exhibit many features considered tell-tale signs of highly intelligent species on our planet including longevity, plasticity, social cohesion and interaction, rudimentary language, sustainable farming abilities, and maintaining sanitary conditions in their self-built complex housing structures. It is difficult to envision how naked mole-rats would reach even higher levels of intelligence in their natural sensory-challenged habitat, but such an evolutionary path cannot be excluded if they would expand their range onto the earth’s surface. Full article

N-Palmitoyl-Glycine-Histidine (Pal-GH) is a novel low molecular weight gelator. In our previous report, ivermectin, a lipophilic drug, was effectively delivered to skin tissue after topical application with Pal-GH as a spray gel formulation, and a much higher skin concentration was confirmed than with the administration of a conventional oral formulation. The objective of this study was to increase the skin permeation of metronidazole (MTZ), a hydrophilic drug, after the topical application of Pal-GH gel. An evaluation of the combined effect of chemical penetration enhancers (CPEs), such as isopropyl myristate (IPM), propylene glycol (PG), ethanol, diethylene glycol monoethyl ether, and dimethyl sulfoxide (DMSO), on skin permeation was also conducted. We found that a 5% Pal-GH gel containing 1% MTZ (F5_MTZ) exhibited a 2.7-fold higher MTZ permeation through excised hairless rat skin than its solution. Furthermore, F5_PG-MTZ and F5_IPM-MTZ further increased the skin permeation of MTZ when compared to F5_MTZ. Interestingly, F5_PG-MTZ enhanced the skin penetration of MTZ, although no enhancement effect was observed for an MTZ solution containing PG. Thus, a Pal-GH formulation containing PG and IPM may enhance the skin permeation of MTZ. Full article

Excised human skin is utilized for in vitro permeation experiments to evaluate the safety and effect of topically-applied drugs by measuring its skin permeation and concentration. However, ethical considerations are the major problem for using human skin to evaluate percutaneous absorption. Moreover, large variations have been found among human skin specimens as a result of differences in age, race, and anatomical donor site. Animal skins are used to predict the in vivo human penetration/permeation of topically-applied chemicals. In the present review, skin characteristics, such as thickness of skin, lipid content, hair follicle density, and enzyme activity in each model are compared to human skin. In addition, intra- and inter-individual variation in animal models, permeation parameter correlation between animal models and human skin, and utilization of cultured human skin models are also descried. Pig, guinea pig, and hairless rat are generally selected for this purpose. Each animal model has advantages and weaknesses for utilization in in vitro skin permeation experiments. Understanding of skin permeation characteristics such as permeability coefficient (P), diffusivity (D), and partition coefficient (K) for each skin model would be necessary to obtain better correlations for animal models to human skin permeation. Full article