Adult Guinea Pigs Research Articles

Electrical Coupling of Heterotypic Ganglion Cells in the Mammalian Retina.

Electrical coupling has been reported to occur only between homotypic retinal ganglion cells, in line with the concept of parallel processing in the early visual system. Here, however, we show reciprocal correlated firing between heterotypic ganglion cells in multielectrode array recordings during light stimulation in retinas of adult guinea pigs of either sex. Heterotypic coupling was further confirmed via tracer spread after intracellular injections of single cells with neurobiotin. Both electrically coupled cell types were sustained ON center ganglion cells but showed distinct light response properties and receptive field sizes. We identified one of the involved cell types as sustained ON α-ganglion cells. The presence of electrical coupling between heterotypic ganglion cells introduces a network motif in which the signals of distinct ganglion cell types are partially mixed at the output stage of the retina.SIGNIFICANCE STATEMENT The visual information is split into parallel pathways, before it is sent to the brain via the output neurons of the retina, the ganglion cells. Ganglion cells can form electrical synapses between dendrites of neighboring cells in support of lateral information exchange. To date, ganglion-to-ganglion cell coupling is thought to occur only between cells of the same type. Here, however, we show that electrical coupling between different types of ganglion cells exists in the mammalian retina. We provide functional and anatomical evidence that two different types of ganglion cells share information via electrical coupling. This new network motif extends the impact of the heavily studied coding benefits of homotypic coupling to heterotypic coupling across parallel neuronal pathways.

Assessment of health status during exposure to cigarette smoke using blood chemistry, lung tissue histology and myocardial metabolism

Background and Objectives: Cardiorespiratory function is critical to well-being. The effect of cigarette smoke exposure (CSE) as a pollutant on human health is of great interest and requires an adequate investigation in order to reduce the burden of its complications. This study was designed to investigate the effect of cigarette smoke on cardiovascular function and airway muscle functional anatomy using an experimental setup. Materials and Methods: Twenty adult male guinea pigs were grouped into four different groups and exposed to different concentrations of cigarette smoke. On the 12th week of exposure, blood pressure parameters were determined with the aid of a pressure transducer connected to a PowerLab data acquisition syste m. Vascular reactivity was also measured in relation to norepinephrine (NE), acetylcholine (ACh), and sodium nitroprusside (SNP). Myocardial oxygen demand (MOD) and baroreceptor reflex sensitivity were equally evaluated. Animals were sacrificed through cervical dislocation, and the lung and trachea were har vested for histological studies. Results: Cigarette smoke significantly decreased blood pressure and heart rate (HR), baroreceptor sensitivity, and MOD (P 0.05). Red blood cell and platelet concentration as well as sodium and calcium level in the blood were all increased at high dose of exposure. Conclusion: CSE resulted in alteration in histological architecture of the lungs and trachea. CSE decreased blood pressure, baroreflex sensitivity, MOD, and vascular reactivity response of MABP to ACh and SNP and increased HR and vascular reactivity response to NE. Furthermore, it also negatively altered the normal architecture of the lung and trachea.

Histomorphological and Histochemical Study of the Uterus of the Adult Guinea Pigs (Cavica porcellus)

Objectives: This study was carried out to identify the histomorphological and histochemical aspects of the uterus in the adult guinea pig (Cavica porcellus). To conduct such project, fourteen adult guinea pigs at their diestrous period were bought from the local breeders directly. Methods: Animals were euthanized, dissected, and subsequently uteruses specimens were collected and fixed by 10% neutral buffered formalin and some specimens were fixed in Bouin’s solution for subsequent histochemical staining. Then after specimens were subjected to routine processes such as dehydration, clearing, embedding, and block preparation. Sections of 6 µm were prepared and stained with haematoxylin–eosin, Masson’s Trichrome, Alcian blue (pH 2.5), and Periodic acid shiff stains. Findings: Gross findings of the uteruses revealed duplex uterus in the guinea pigs. It possessed two separate uterine horns united caudally to form the body, suspended by mesometrium in the abdominal cavity. Caudally, body formed the cervix, which was short and projected into the vaginal cavity forming portio vaginalis uteri with one cervical orifice.Microscopic findings revealed abrupt changes in the wall of the isthmus into the uterine horn at the utero-tubal junction. The wall of the uterus showed endometrium, vascular layer, myometrium, and adventitia or serosa. Lining epithelium was simple columnar which was similarly lined the endometrial glands. Myometrium was consisted of inner circular and outer longitudinal bundles of smooth muscle fibers. In the body, the lining epithelium was replaced gradually by simple mucous columnar epithelium. In addition to that the mucosa was thrown into long folds leaving small lumen at the cervix called os cervix. Such changes were associated with endometrial glands gradual diminishing till the cervix. Histochemically, the non-ciliated columnar cells present in the body and cervix were stained positively with AB (pH 2.5) and PAS stains. The reaction with AB (pH 2.5) was more intense compared with the staining with PAS so that it indicated that mucin was more acidic than neutral in nature.Keywords: Guinea Pig, Uterus, Diestrous, Histochemistry

The effect of pulmonary surfactant on the airway smooth muscle after lipopolysaccharide exposure and its mechanisms.

Pulmonary surfactant has a relaxing effect on the airway smooth muscle (ASM), which suggests its role in the pathogenesis of respiratory diseases associated with hyperreactivity of the ASM, such as asthma and chronic obstructive pulmonary disease (COPD). The ASM tone may be directly or indirectly modified by bacterial wall component lipopolysaccharide (LPS). This study elucidated the effect of LPS on the ASM reactivity and the role of surfactant in this interaction. The experiments were performed using ASM of adult guinea pigs by in vitro method of tissue organ bath (ASM unexposed-healthy or exposed to LPS under in vitro conditions) and ASM of animals intraperitoneally injected with LPS at a dose 1 mg/kg of b.w. once a day during 4-day period. Variable response of LPS was controlled by cyclooxygenase inhibitor indomethacin and relaxing effect of exogenous surfactant was studied using leukotriene and histamine receptor antagonists. The exogenous surfactant has relaxing effect on the ASM, but does not reverse LPS-induced smooth muscle contraction. The results further indicate participation of prostanoids and potential involvement of leukotriene and histamine H1 receptors in the airway smooth muscle contraction during LPS exposure.

Histological and immunohistochemical study on the effect of valporic acid on the bone of adult male guinea pigs and the possible protective role of L-carnitine

Background: Valporic acid (VPA) is a broad-spectrum antiepileptic drug and is effective in the treatment of different types of epileptic seizures. It usually affects bone and mineral metabolism and increase the risk of fractures due to decreased bone mineral density (BMD). Among dietary supplements, L-carnitine is an emergic candidate with potential bone protective effects. It promotes energy utilization and is important for tissues with high energy requirements.Objective: The target of this work is to estimate the effect of valproic acid on the femur and the possible protective effect of L-carnitine administration in adult male guinea pigs.Materials & Methods: Forty adult male guinea pigs were utilized in the current study. The guinea pigs were divided into four groups, Group I (control group), Group II(L-carnitine treated group), Group III (Valporic acid treated group) and Group IV (L-carnitine and valporic acid treated group). After 10 weeks, the upper parts of femur were processed for histological, morphological and immunohistochemical studies.Results: Valporic acid treated group was associated with enhanced bone turnover as evident by a significant change in serum levels of calcium, osteocalcin and TRAP. Moreover, there was a significant decrease in trabecular and cortical bone thickness and a significant change in the mean number of osteoclasts and osteoblasts. Histologically, evidence of bone resorption was manifested in the femoral bone with resorption cavities, irregular endosteal surface. Decrease of collagen in the cortical bone was evident in trichrome-stained sections. Immunohistochemically, this group showed positive immunoreactivity for caspase-3 in osteocytes and decrease in osteopontin expression in bone matrix. L-carnitine supplementation with valporic acid in group IV has ameliorating effect on the histological abnormalities of bone.Conclusion: L-carnitine improved the biochemical, histological and morphometric changes induced by VPA, and therefore, there is a potential benefit in using L-carnitine with long term administration of valporic acid.

The preparation of dexamethasone sodium phosphate multivesicular liposomes thermosensative hydrogel and its impact on noise-induced hearing loss in the Guinea pigs

ObjectiveThe aim of this study is to establish the dexamethasone sodium phosphate multivesicular liposomes thermosensative hydrogel (DEX-MVLs-Gel) drug delivery system and to analyze the pharmacodynamics, pharmacokinetics and safety of DEX-MVLs-Gel as well as to explore whether the prepared DEX-MVLs-Gel can protect the hearing in the guinea pigs following noise exposure. MethodsDEX-MVLs formulations were constructed by double emulsion method, and the DEX-MVLs-Gel was prepared after adding P407 and P188 into the DEX-MVLs. A total of 20 adult albino guinea pigs were chosen to establish the animal models with noise-induced hearing loss. After animals were treated with DEX-MVLs-Gel at concentrations of 20, 6 and 2 mg/mL, and 5 mg/mL Dexamethasone Sodium Phosphate (DEX-P) solution, respectively, the hearing function, drug concentration in the peripheral lymph fluid, and hair cell morphology were assessed. ResultsThe ABR threshold of the 20 mg/mL DEX-MVLs-Gel treated group at the frequencies of 4, 8, 16 and 24 kHz were measured as 47.5 ± 5.2, 48.3 ± 4.1, 55.8 ± 3.8 and 57.5 5 ± 5.2 dB SPL, respectively. Statistical significances were noted between the 20 mg/mL DEX-MVLs-Gel treated group and control group at each frequency (all P < 0.05), between the 2 mg/mL and 6 mg/mL DEX-MVLs-Gel treated groups at the frequencies of 4 and 8 kHz (both P < 0.05). High Performance Liquid Chromatography (HPLC) demonstrated that the drug concentrations in the peripheral lymph in all groups were gradually decreased on the 1st, 3rd and 7th d after intratympanic injection. Scattered hair cell loss could be observed mainly in the basal and middle turn in the saline administrated group and the 20 mg/mL DEX-MVLs-Gel administration group, and the hair cell loss was not identified in the apical turn. ConclusionsA high concentration (20 mg/mL) of DEX-MVLs-Gel exerts significant protective effects upon the guinea pigs with noise-induced hearing loss. The prepared DEX-MVLs-Gel can be effectively maintained in the peripheral lymph fluid of guinea pigs for 3–7 d and MVLs-Gel causes no obvious ototoxicity.

Fetal Growth Restriction Is Associated With Decreased Number of Ovarian Follicles and Impaired Follicle Growth in Young Adult Guinea Pig Offspring

The mechanisms mediating the impacts of fetal growth restriction (FGR) on follicular development are commonly studied in mouse/rat models, where ovarian development occurs largely during the early postnatal period. These models have shown that FGR is associated with premature follicle loss, early pubertal onset, and accelerated ovarian aging. Whether the same occurs in precocious species is unknown. Since guinea pig follicle development occurs in utero in a manner consistent with human ovarian development, we sought to determine whether FGR had similar impacts on guinea pig ovarian development. Dunkin-Hartley guinea pig dams were randomized to receive a control (CON) or a nutrient-restricted diet (FGR) prior to conception until weaning. Offspring ovaries were collected at prepubertal (postnatal day [P] 25) and young adult (P110) time points. Prepubertal offspring exposed to FGR showed little differences in ovarian transcript levels and follicle counts. Young adult FGR offspring, however, showed reductions in the number of transitioning, primary, and antral follicles, as well as corpora lutea. This loss in follicles was associated with reduced insulin-like growth factor receptor and growth differentiation factor-9 messenger RNA levels in FGR P110 offspring compared to CON. We demonstrate that FGR in guinea pigs is accompanied by perturbations in signaling pathways essential for proper follicle growth and manifests as reductions in growing follicles in offspring, but these changes do not manifest until postpuberty. These data support the fact that accelerated reproductive maturation/aging is a conserved phenotype that is associated with in utero nutritional adversity.

Modeling dermatophytosis: Guinea pig skin explants represent a highly suitable model to study Trichophyton benhamiae infections.

Dermatophyte infections are a growing health concern worldwide with increasing patient numbers, especially in children. However, detailed knowledge about infection mechanisms and virulence factors are scarce. This study aimed to establish an infection model based on guinea pig skin explants mimicking the in vivo situation as closely as possible to survey the pathogenesis of dermatophytoses. A fundamental prerequisite was the detailed description of native guinea pig skin and its morphological changes during tissue culture because comprehensive data on guinea pig skin characteristics were not available. Skin explants were harvested from healthy, adult guinea pigs and transferred to cell culture inserts. One group was inoculated with defined suspensions of colony-forming units of zoonotic Trichophyton benhamiae isolates; others served as controls to assess the tissue viability during the 10-day culture. Samples were taken on days 3, 5, 7 and 10 and processed for histological and immunohistochemical analysis. Standard tissue culture conditions provoked acantholysis and regional orthokeratotic alterations. The reduced desquamation caused hyperkeratosis paralleled by hypogranulosis or regional hyperplasia. During T.benhamiae infection, keratinocyte proliferation came to a complete halt on day 5 whereas the number of terminal deoxynucleotidyl transferase dUTP nick end labeling assay-positive cells increased moderately up to day 7. Hyphae grew massively into the skin explants causing strong keratinolysis and tricholysis. By the end of the culture, complete disintegration of the basement membrane and dermal tissue was observed. A realistic and reliable skin infection model was established to study dermatophytoses in general and cutaneous T.benhamiae infections in particular.

Guided growth with aligned neurites in adult spiral ganglion neurons cultured in vitro on silicon micro-pillar substrates

Objective. Assessment of the relationship between the topographical organization of silicon micro-pillar surfaces (MPS) on guidance and neural alignment of adult spiral ganglion neurons (SGN) and use of the otosurgical approach as an alternative for the extraction and isolation of SGNs from adult guinea pigs. Approach. SGNs from adult guinea pigs were isolated using conventional and otosurgical approach for in vitro cell culturing on MPS of various micro-pillar widths (1–5.6 µm) and spacing (0.6–15 µm). Cell cultures were compared morphologically with neuronal cultures on control glass coverslips. Main results. We found enhanced SGN in vitro cultures in MPS areas with small and intermediate inter-pillar spacing (from 0.6 µm to 3.2 µm) as well as in MPS areas with wider pillars (from 1.8 µm to 4 µm) compared to MPS flat zones and control glass coverslips. Scanning electron microscopy (SEM) images highlighted how neurites of SGNs follow straight lines by growing on top and between micro-pillars. Only micro-pillars with small and intermediate pillar spacings favor neurite alignment along preferred angles (30°, 90°, and 150°), while pillars with wider spacing produced less aligned neurites. We found propensity of adult SGNs grown on MPSs to attain more bipolar and multipolar morphologies. Additionally, we observed reduced interaction between neuronal and glial cells compared to control glass coverslips. Finally, we found that the otosurgical approach was more beneficial for SGN survival on glass coverslips and MPS flat surfaces than the conventional method. Significance. MPS with specific architecture supports the guided growth of adult SGNs in vitro and controls adult SGN development and behavior.

EKSTRAK KULIT BUAH MANGGIS (Garcinia Mangostana L.) SEBAGAI OBAT ANTI DIARE

This study aims to determine whether mangosteen rind extract (in the form of ethanol extract/EE) can be used as an anti-diarrhea drug after compared with other anti-diarrhea substances in three experimental groups. This research is an in vitro experimental study using adult male guinea pigs weighing 400-600 gr through the standard method of Magnus with the Latin square controlled experiment design. The study was conducted at the Pharmacology and Toxicology Laboratory of the Faculty of Pharmacy, University of North Sumatra. The results showed that the contraction of ileum in Ach with Atp + Ach compared the difference in contraction of ileum Ach with EE + Ach showed the difference in difference between the two contractions of the ileum was significant, the contraction of ileum in His with Dip + His compared indifference in contraction of ileum His with EE + His showed a difference indifference. the two ileal contractions are significant, the ileal contraction in the bar with Papa + Bar compared to the difference between the ileum bar contraction with EE + Bar shows no difference in the difference between the two ileum contractions. The conclusion is that the Mangosteen Skin Ethanol Extract works similarly to Papaverine Hydrochloride which is an antidiarrheal drug used to relax smooth muscles so that it can also make blood vessels dilate by relaxing smooth muscles in the walls of blood vessels.

Cardiac Pacemaker Cells Generate Cardiomyocytes from Fibroblasts in Long-Term Cultures

Because cardiomyocyte generation is limited, the turnover of cardiomyocytes in adult heart tissues is much debated. We report here that cardiac pacemaker cells can generate cardiomyocytes from fibroblasts in vitro. Sinoatrial node cells (SANCs) were isolated from adult guinea pig hearts and were cultured at relatively low cell densities. Within a week, a number of fibroblast-like cells were observed to gather around SANCs, and these formed spontaneously beating clusters with cardiomyocyte structures. The clusters expressed genes and proteins that are characteristic of atrial cardiomyocytes. Pharmacological blocking of pacemaker currents inhibited generation of action potentials, and the spontaneous beating were ceased by physically destroying a few central cells. Inhibition of beating during culture also hampered the cluster formation. Moreover, purified guinea pig cardiac fibroblasts (GCFs) expressed cardiac-specific proteins in co-culture with SANCs or in SANC-preconditioned culture medium under electrical stimulation. These results indicate that SANCs can generate cardiomyocytes from cardiac fibroblasts through the influence of humoral factor(s) and electrophysiological activities followed by intracellular Ca2+ oscillations. This potential of SANCs to generate cardiomyocytes indicates a novel mechanism by which cardiomyocytes turns over in the vicinity of pacemaker cells and could be exploited in the development of strategies for cardiac regenerative therapy in adult hearts.

Electrode impedance changes after implantation of a dexamethasone-eluting intracochlear array

Postoperative inflammation and the formation of fibrotic tissue around the intracochlear electrode array are often held responsible for negative outcomes in cochlear implant recipients. Here we test the effectiveness of intracochlear delivery of dexamethasone via a drug-eluting electrode array in reducing fibrotic tissue formation, assessed via measurement of both monopolar and four-point electrode impedance. Adult guinea pigs were bilaterally implanted with a dexamethasone-eluting array (left ear) and a standard non-eluting array (right ear). Arrays were electrically stimulated daily for 4 weeks, commencing 1 week after implantation, and impedance measured both before and after stimulation. Histological assessment of the tissue was made at the end of the 5-week period. The dexamethasone-eluting array did not reduce monopolar (MP1 + 2) electrode impedance over the course of 5 weeks, and no significant difference was observed in fibrotic tissue, new bone growth, or spiral ganglion neuron density between array types. However, four-point impedance, which provides an indication of the local environment at the neural-tissue interface, was significantly lower in the presence of dexamethasone. A strong relationship was seen between four-point and monopolar impedance for individual electrode arrays, with the exception of the standard array after daily electrical stimulation. This group instead showed a significant correlation between the final four-point impedance measure and percentage of fibrous tissue and new bone growth. In conclusion, this study demonstrated that dexamethasone influences four-point electrode impedance as well as the relationship between fibrotic tissue and impedance, and that both outcomes are shaped by daily electrical stimulation. These results suggest a change occurs at the local tissue-electrode interface in the presence of sustained, intracochlear release of dexamethasone.

Histomorphological and Histochemical Study of the Ovary and the Uterine Tubes of the Adult Guinea Pigs (Cavica porcellus)

This study was carried out to identify the histological structures of the ovary and the related uterine tubes of the adult guinea pig (Cavica porcellus). To conduct such project, 14 adult guinea pigs at their diestrous period were collected from the local breeders directly. Animals were euthanized, dissected and subsequently ovaries and specimens from uterine tubes were collected and fixed by 10% neutral buffered formalin and some of specimens were fixed in Bouin’s solution for subsequent histochemical staining then subjected to routine processes such as dehydration, clearing, embedding and block preparation. Sections of 6 µm were prepared and stained with hematoxylin-eosin, Masson’s Trichrome, Alcian blue (pH 2.5) and Periodic acid shift stains. Gross findings showed two bilateral rounded and slightly elongated ovaries situated in the abdominal cavity suspended by mesovarium ligament. Microscopic findings revealed prominent large follicles and to a lesser extent, the small and medium types in the ovaries of adults studied guinea pigs. The data showed the presence of many pre-ovulatory follicles during the diestrous period in this polyestrous species. Gross findings of the uterine tubes revealed the presence of bilateral uterine tubes. Each tube included short straighten preampulla which was expanded cranially to form infundibulum, coiled long ampulla and finally the isthmus, the shortest and straight part traversed the cranial end of the uterine horn. Microscopically, all of the uterine tube was lined with simple columnar epithelium. Mucosa showed very long and branched mucosal folds in the pre-ampulla, for lesser extent in ampulla but shortest and widest in isthmus. Tunica muscularis was absent at infundibulum, thinnest at pre-ampulla, whereas, the thickest in isthmus. Histochemically, the non ciliated columnar cells (present mainly in the isthmus and few in ampulla) were stained positively with AB and PAS stains.

Histoarchitecture of Islet’s of Langerhans and Their Related Hormones Analysis in the Pancreas of Adult Guinea Pig (Cavia porcellus)

The present study was conducted to study the endocrine portion of the pancreas represented by Islets of Langerhans in the adult males and females guinea pigs. Eight animals of each sex were collected to conduct these aims. Histological sections prepared from the specimens which were collected from three identified lobes of the pancreas and subsequently fixed by 10% neutral buffered formalin. Post conducting the routine histological procedure on specimens, three stains were used such as hematoxylin and eosin, Masson’s trichrome and Gomori's Aldehyde trichrome for identification of cellular composition of the pancreatic Islet's of Langerhans. The endocrine islets showed predominantly s, and for a lesser extent α cells. The δ cells were rarely detected. The percentage of s cells in the islets of male pancreas was higher than those in females. On contrary, the percentage of α cells was higher in the islets of females than those in the males. Such findings were proportional to hormones analysis of insulin and glucagon which were corresponding products to these cells. In conclusion, Percentage of s cells in the islets of male pancreas was higher than that in females. On the contrary, the percentage of α cells was higher in the islets of females than that in the males. Such observations were parallel positively with hormones analysis of insulin and glucagon which were corresponding products to these cells.

Mechanisms of electrical remodeling in lipotoxic guinea pig heart

ObjectivesTo develop an adult guinea pig model of lipotoxicity and explore the underlying mechanisms associated with changes in the expression of the delayed rectifier potassium current (IK). BackgroundLipotoxicity may represent a common link among metabolic disorders and a higher vulnerability to arrhythmias. MethodsWhole-cell patch clamp, and palmitic acid (PA, a potent inducer of lipotoxicity), were used to assess mechanisms of short-term (∼50 days) high-fat diet (HFD) feeding on atrial electrophysiology in guinea pig hearts and myocytes. ResultsHFD fed guinea pigs were significantly heavier, displayed hypertriglyceridemia and hypercholesterolemia; but no signs of hyperglycemia or inflammation compared to low-fat diet fed controls. Increasing cardiac PA levels, resulted in shortened atrial action potential duration, and increased IK density. Inhibition of phosphoinositide 3-kinase (PI3K) prevented increases in IK due to PA. Acute (≥1hr) exposure of atrial myocytes to exogenous PA (1 mM) increased the density of the rapid delayed rectifier potassium current IKr, while it was decreased with the unsaturated oleic acid (OA, 1 mM). Serine-threonine protein phosphatase-2 (PP2A) inhibition with cantharidin reversed the effect of OA on IKr. ConclusionOur data provide evidence of a novel lipotoxic guinea pig model with signs of vulnerability to arrhythmias. Inhibition of PA/PI3K/IK and/or activation of the OA/PP2A/IKr pathways may be therapeutically beneficial for lipotoxic arrhythmias.

Three-dimensional modelling of the femur and humerus in adult male guinea pigs (guinea pig) with computed tomography and some biometric measurement values.

Guinea pig is a species belonging to the Caviidae family of the Rodentia order and is frequently used in experimental studies. Biomedical imaging methods are used in the diagnosis and treatment of many diseases in medicine. Among these methods, computed tomography (CT) is one of the most important imaging methods. In this study, it was aimed to perform the three-dimensional (3D) modelling of the CT images, obtained from the humerus and femur in the guinea pigs, via the MIMICS programme, and to make some biometric measurements regarding the bones over these models. In the present study, 12 male adult guinea pigs were used. The soft tissue on the humerus and femur bones of the guinea pigs was removed. After this procedure, CT images at a 0.5 mm-thickness were obtained from the animals. The images were recorded in DICOM format. Then, the reconstruction process was performed from the images by using the 3D modeling programme MIMICS® 13.1. On the 3D model of the humerus and femur (right-left), volumes, surface areas and lengths as well as other biometric parameters were measured separately, and the values were recorded. In addition, measurements of the bones were made with the help of a digital calliper. Among the parameters obtained from 3D models, a statistical difference was observed between the right and left cortical thicknesses of the femur from the measurements of calliper and the right and left humerus volumes (p < 0.05); whereas, no statistical difference was found in other parameters of both measurements (p > 0.05). It can be stated that CT and 3D modelling can be used for the measurement of some parameters in the long bones of the guinea pigs.

Expression pattern of Connexin 26 and Connexin 30 in mature cochlea of the monkey

Connexin26 (Cx26) and Cx30 are the predominant connexin subtypes found in the cochlea. They play an essential role in the cochlear functions. However, most studies use mice and the data on the cochlear expression profiles of the two Cxs in higher animals (e.g., humans) are scarce. Studies using the cochleae from non-human primate other than mice may provide information needed to narrow this gap. Here we studied cellular distributions of Cx26 and Cx30 in the adult monkey and guinea pig cochleae by immunofluorescent labeling and confocal microscopy observations. We detected Cx26 and Cx30 expressions in the type I, II& V fibrocytes in the spiral ligament, fibrocytes of the spiral limbus, in the supporting cells of organ of Corti, inner and outer sulcus cells, and in the basal cells of the stria vascularis. Both Cx26 and Cx30 were not detected in hair cells, in mesenchymal cells under the basilar membrane and cells lining the scala vestibule. Cells of the Reissner's membrane and spiral ganglion neurons are also negative. These findings demonstrate that cochlear expressions of Cx26 and Cx30 in the adult mouse, guinea pig and non-human primate have a common cellular pattern.

Anatomical and histological study of kidney, ureter and urinary bladder in male guinea pig (Cavia porcellus)

A total of 20 healthy adult male guinea pigs were used in this study to investigate the anatomical, histological and morphometrical characteristics of the kidneys, ureter and urinary bladder. The gross anatomical study showed that the right kidney had a bean shape with reddish pink color whereas the left kidney had a heart shape. The renal cortex appeared darker than medulla with reddish brown color, while the medulla was pale in color. The mean thickness of cortex was more than that of medulla in both left and right kidneys and the ratio of cortex to medulla was 1.06: 1 in both kidneys. The mean length of right ureter was 10.3±0.62 cm while the mean length of left ureter was shorter. The filled urinary bladder appeared as a pear-shaped hollow sac situated in the pelvic cavity and only the rounded cranial part of bladder was expanded. Four histological regions of renal tubules were found in kidney. The Proximal convolutes tubule is first longest and coiled segment of renal tubules which originate from urinary pole of renal corpuscles and measured about 25.421±0.3µm in diameter and lined with simple cuboidal epithelial cells. The Nephron loop (Loop of Henle) was consisted of the descending and ascending thin limbs, the descending thin limb was measured 13.591±0.1µm diameter, whereas the thick ascending limb was measured (19.987±0.5µm) in diameter. Distal convolutes tubule was shorter than the proximal tubule and measured about 21.139±0.5µm diameter. The collecting duct was measured about (31.759±0.2µm) diameter. It was lined with simple cuboidal or columnar epithelium. The cross section of Ureter was possessed a star shape lumen and its wall consist from four tunics (mucosa, lamina propria submucosa, muscularis and serosa). It was lined by transitional epithelium. The histological structure of Urinary Bladder was resembles the ureter, the lamina propria contain few mucous glands.

Adult vascular dysfunction in foetal growth-restricted guinea-pigs is associated with a neonate-adult switching in Nos3 DNA methylation.

Foetal growth restriction (FGR) is associated with endothelial dysfunction and cardiovascular diseases in adult subjects. Early vascular remodelling and epigenetic changes occurring on key endothelial genes might precede this altered vascular function. Further, it has been proposed that oxidative stress during development may determine some of these epigenetic modifications. To address this issue, we studied the in vivo and ex vivo vascular function and Nos3 promoter DNA methylation in arteries from eight-month-old guinea-pig born from control, FGR-treated and FGR-NAC-treated pregnancies. Femoral and carotid arteries in vivo vascular function were determined by Doppler, whilst ex vivo vascular function and biomechanical properties were assessed by wire myography. Levels of eNOS mRNA and site-specific DNA methylation in Nos3 promoter in aorta endothelial cells (AEC) were determined by qPCR and pyrosequencing respectively. FGR adult showed an increased femoral vascular resistance (P<.05), stiffness (P<.05) and arterial remodelling (P<.01), along with an impaired NO-mediated relaxation (P<.001). These effects were prevented by maternal treatment with NAC. Endothelial-NOS mRNA levels were decreased in FGR adult compared with control and FGR-NAC (P<.05), associated with increased DNA methylation levels (P<.01). Comparison of Nos3 DNA methylation in AEC showed a differential methylation pattern between foetal and adult guinea-pigs (P<.05). Altogether, these data suggest that adult vascular dysfunction in the FGR does not result from early changes in Nos3 promoter DNA methylation, but from an altered vessel structure established during foetal development.

Mast Cell Degranulation and Fibroblast Activation in the Morphine-induced Spinal Mass: Role of Mas-related G Protein-coupled Receptor Signaling.

As the meningeally derived, fibroblast-rich, mass-produced by intrathecal morphine infusion is not produced by all opiates, but reduced by mast cell stabilizers, the authors hypothesized a role for meningeal mast cell/fibroblast activation. Using the guinea pig, the authors asked: (1) Are intrathecal morphine masses blocked by opiate antagonism?; (2) Do opioid agonists not producing mast cell degranulation or fibroblast activation produce masses?; and (3) Do masses covary with Mas-related G protein-coupled receptor signaling thought to mediate mast cell degranulation? In adult male guinea pigs (N = 66), lumbar intrathecal catheters connected to osmotic minipumps (14 days; 0.5 µl/h) were placed to deliver saline or equianalgesic concentrations of morphine sulfate (33 nmol/h), 2',6'-dimethyl tyrosine-(Tyr-D-Arg-Phe-Lys-NH2) (abbreviated as DMT-DALDA; 10 pmol/h; μ agonist) or PZM21 (27 nmol/h; biased μ agonist). A second pump delivered subcutaneous naltrexone (25 µg/h) in some animals. After 14 to 16 days, animals were anesthetized and perfusion-fixed. Drug effects on degranulation of human cultured mast cells, mouse embryonic fibroblast activation/migration/collagen formation, and Mas-related G protein-coupled receptor activation (PRESTO-Tango assays) were determined. Intrathecal infusion of morphine, DMT-DALDA or PZM21, but not saline, comparably increased thermal thresholds for 7 days. Spinal masses proximal to catheter tip, composed of fibroblast/collagen type I (median: interquartile range, 0 to 4 scale), were produced by morphine (2.3: 2.0 to 3.5) and morphine plus naltrexone (2.5: 1.4 to 3.1), but not vehicle (1.2: 1.1 to 1.5), DMT-DALDA (1.0: 0.6 to 1.3), or PZM21 (0.5: 0.4 to 0.8). Morphine in a naloxone-insensitive fashion, but not PZM21 or DMT-DALDA, resulted in mast cell degranulation and fibroblast proliferation/collagen formation. Morphine-induced fibroblast proliferation, as mast cell degranulation, is blocked by cromolyn. Mas-related G protein-coupled receptor activation was produced by morphine and TAN67 (∂-opioid agonist), but not by PZM21, TRV130 (mu biased ligand), or DMT-DALDA. Opiates that activate Mas-related G protein-coupled receptor will degranulate mast cells, activate fibroblasts, and result in intrathecal mass formation. Results suggest a mechanistically rational path forward to safer intrathecal opioid therapeutics.