Caffeine (Caf) is largely used to delay fatigue, improving physical activity. However, its role remains elusive, and there are no hemodynamic or immunohistochemical data regarding its effects on ...skeletal muscle. We studied the hemodynamic and NOS expression of Bax/Bcl2 in skeletal muscle after single Caf administration. Thirty-two male rats were divided into six groups: the first was iv-injected with Caf (16
mg/kg), the second with Caf
+
L-NAME, the third with Caf
+
L-arg, the fourth with Caf
+
L-NAME
+
L-arg, fifth with saline. Mean arterial blood pressure (MAP) was monitored for 30′, then the animals were killed. The sixth group was injected with Caf and killed after 2
h. The quadriceps were isolated and processed by immunohistochemistry. We found that Caf increased MAP temporarily, while Caf
+
L-NAME increased it for a longer period. In untreated muscle, all NOS isoforms was expressed with different intensity and localisation, and Bcl2 was strongly expressed among the myofibrils. In Caf and Caf
+
L-NAME treated animals, NOS expression was lost; Bcl2 expression decreased among myofibrils but increased inside the subsarcolemma. The L-arg administration reversed these Caf and L-NAME effects. Two hours after Caf, NOS expression increased. We concluded that improved physical performance could be related to Caf's ability to interfere with the endogenous muscular synthesis of NO.
Trigeminal hyperalgesia frequently appears in diabetic neuralgia altering the transmission of orofacial sensory information. This study was designed to explore the effects of trigeminal hyperalgesia ...in streptozotocin-induced diabetes monitoring the expression of nitric oxide synthase in the trigeminal ganglion cells. The threshold to heat noxious stimuli decreased in diabetic animals. The number of NADPH-diaphorase (NADPH-d)-positive neurons significantly decreased in the diabetic rats compared with controls. Insulin treatment prevented the decreased nociceptive threshold and reduction of the number of NADPH-d-positive neurons. These findings point out that there is a relationship between the trigeminal nociceptive perception and NADPH-d neuronal expression suggesting that NO may play a role in the pathogenesis of trigeminal sensory neuropathy.
The aim of this study was to evaluate the adverse effects of cyclosporine A (CsA) toward renal morphogenesis and to test the renoprotective natural antioxidants such as provinol (PV). Pregnant rats ...were divided into four groups. Group I was injected SC with olive oil. Group II was treated with oral administration of PV and was used as control. Group III animals were injected SC daily with CsA, and group IV animals were injected daily with CsA and PV for 21 days of pregnancy. Five pups per litter were killed and the kidneys removed and treated by morphological and immunohistochemical (IHC) methods. IHC analysis considered two proteins responsible for nephrotoxicity in adult rats: inducible nitric oxide (iNOS) and matrix metalloproteinase-2 (MMP2). Pregnancy outcomes among CsA-treated rats demonstrated a reduced number of pups. Pups that were exposed antenatally to CsA presented several pathologic findings in all immature parenchyma and an increase in iNOS and MMP2 expression. These side effects were not observed in kidney of litters born from CsA + PV-treated mothers. Our study indicates that CsA induces morphological alterations in renal parenchyma of neonates and that PV plays a protective role against these side effects.
Glass‐fiber composites are frequently used in dentistry. In order to evaluate their biocompatibility we tested, in an experimental model “in vivo”, their tissue response pointing our attention on ...presence of mast cells (MCs) and fibrotic process. Sprague Dawley rats were used for the experimental design. The fibers were introduced in a subcutaneous pocket along the middle dorsal line between the two scapulas for 7, 14 or 21 days. At the end of the treatments the skins were excised and then processed for Toluidine Blue, to determine the presence of MCs, and Picrosirius Red staining, to evaluate the presence of fibrotic tissue. Our preliminary results showed and increase of both MC number and deposition of collagen type I, which characterized the fibrotic tissue. So, subsequent aims of our study were to evaluate the role played by MCs in tissue fibrosis and to give a possible explanation regarding the mechanisms that were responsible of biological response observed, through the analyses of some proteins, such as metalloproteinase‐2 (MMP‐2), its inhibitor (TIMP‐2) and transforming growth factor‐β (TGF‐β). Our data confirmed the involvement of TGF‐β, released by MCs, in the disruption of the equilibrium between MMP‐2 and TIMP‐2 that were implicated in the enhancement of fibrosis. In summary, this study demonstrate that this type of materials induced an inflammatory response at the site of implant and help to clarify what type of mechanism and which proteins are involved in this biological response. Nevertheless, more extensive investigations are in progress to better evaluate the inflammatory process.
In this study we examined the effects of the glutamate metabotropic subtype 5 (mGlu5) receptor antagonist 2
-methyl-6-(phenylethynyl)-pyridine (MPEP) on Fos expression in the spinal cord in a model ...of visceral pain in the rat. We show that noxious stimulation increases the number of Fos-positive neurons in the dorsal horn of the thoracic and lumbar spinal cord, and that pretreatment with MPEP significantly reduces the number of Fos-positive neurons in these areas. These data indicate that mGlu5 is involved in the transmission of visceral pain in the spinal cord.
Aluminium (Al) exposure is neurotoxic and is considered a possible etiological factor for many neurodegenerative disorders. Since it is known that Al impairs the glutamate–nitric oxide–cGMP pathway ...in neurons, this study was carried out to monitor the expression of NADPH-d in some central nervous system areas of rats after chronic administration of Al in drinking water. We tested three different nervous areas known to contain NADPH-diaphorase positive neurons: two cortical area (somatosensory cerebral cortex and cerebral cortex), a deep brain area (dorsolateral periaqueductal gray matter) and a spinal area (lumbar enlargement of the spinal cord). Our data showed that Al significantly decreased NADPH-d positive neurons in the cerebral cortex and the NADPH-d staining of many granular neurons in the cerebellum. We also found that Al did not cause neuron loss or apoptosis in the cerebral cortex. These findings suggest that the cortical nitroxidergic neurons and granule cells were a specific target of Al neurotoxicity.
Mercuric chloride (HgCl 2 ) produces an acute renal failure in experimental animal models. Since the mechanism of tubular injury has not completely been clarified, this morpho-quantitative study was ...undertaken to better understand the effects of 2 sublethal doses (T1=1 mg/kg and T3.5=3.5 mg/kg) of HgCl 2 in rat proximal tubules. Morphometrical analysis was performed to quantify both cytoplasmic and nuclear changes found in treated in respect to saline-injected proximal tubules. In the controls, single-cell damage was occasional and nucleolar changes were absent. HgCl 2 induced progressively severe proximal tubule atrophy. In the T1 group, necrosis was limited to pars recta cells and nucleolar segregation was often partial. In the T3.5 group, atrophy was extensive in both convoluted and straight tracts, the nucleolus was completely segregated and coiled body-like inclusions were detached from it. Ultrastructural analysis confirmed dose-dependent changes within straight proximal tubules, i.e., necrosis, apoptosis, nucleolar segregation, swollen mitochondria, vacuolization, and disrupted brush border. In conclusion, in the rat kidney HgCl 2 induced dose-dependent alterations not only in the cytoplasm but also in the nucleus of proximal tubule cells. These findings will be useful for better understanding of the pathogenesis of mercury nephrotoxicity and its genotoxic effect.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The immunosuppressive drug Cyclosporine A (CsA) has been successfully used in several diseases with immunological basis and in transplant patients. However, the therapeutic treatment induces several ...side effects, which include the development of severe hypertension, renal failure and cardiotoxicity in the majority of the patients. Since the mechanism by which CsA induces hypertension is not well defined, the aim of this study is to evaluate the morphological changes and the expression of heat shock proteins (HSPs) in the thoracic aorta of CsA-treated rats. The study was carried out on 40 male Wistar rats with an average weight of 200–250 g. The animals were divided into four groups. Groups I and II were injected subcutaneously (sc) daily with castor oil for 15 or 30 days and used as control; group III and IV were injected sc daily with CsA (15 mg/Kg/day) for 15 or 30 days. After the end of the treatment, the thoracic aortae were removed and treated for morphological (Sirius Red) and immunohistochemical evaluation (HSP 25, αB-crystallin and HSP 47). The results indicate that CsA induces (1) time-dependent vascular damage visible as fibrosis mainly in intima-media tunica of aorta, and (2) a clear increase in HSP expression. In fact, after 30 days of treatment, HSP and αB-crystallin are increased in all tunicas, whereas HSP47 only in tunica media and adventitia. These findings could suggest that these proteins are up-regulated after CsA treatment in order to play a defensive role in vascular damage.
The human thymuses, the well differentiated carcinoma, the thymoma with spindle epithelial cells and the undifferentiated thymoma have been examined by histochemical techniques lactate dehydrogenase ...(LDH), succinate dehydrogenase (SDH), acid phosphatase (AcP), alkaline phosphatase (ALP) and dihydrofolate dehydrogenase (DHFR) to study the metabolic changes due to the pathological conditions in the epithelial cells (EPCs) and accessory cells. In all three different types of studied thymomas the EPCs showed a more intense LDH and SDH positivity than in normal thymus. These data indicate a possible damage of respiratory chain energy-coupling mechanism. The EPCs presented a different pattern (negative or very strong) of ALP and AcP positivity both in normal and pathological thymuses. These results suggest that the EPCs are a heterogenous population presenting a variety of functional activities both in normal and pathological conditions. The macrophages showed a different pattern (very weak, weak and moderate) in dehydrogenase and in hydrolytic enzymes both in normal and tumour cells. The macrophages were uniformly distributed throughout the thymoma but it is interesting to note that in the well differentiated thymomas these cells were localized in high number only around the neoplastic nodules that were proliferating. These findings suggest that the macrophages are important for defending the organism against the formation of new neoplastic nodules.
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