A comparison of histamine effects on the sympathetic neurotransmission of testicular capsule and rat vas deferens

Histamine is an important modulatory agent of the sympathetic neurotransmission, but its exact action on the testicular capsule or rat vas deferens is not fully understood. The present study sought to further investigate the functional effects of histamine on the neuronal and exogenous noradrenaline-induced contraction of the testicular capsule and rat vas deferens as well as to evaluate the contractile properties of this drug. The testicular capsule or vas deferens from Wistar rats, 3–4 months old, weighing 300–400 g, was isolated and mounted in organ baths for functional experiments. The results indicated that the neuronally evoked contraction of the testicular capsule was affected by histamine (10^?10 to 10^?8 M) with participation of inhibitory (H₃ receptors) and excitatory (H₁ receptors) receptors. Histamine (10^?7 to 10^?4 M) modulated the field-stimulated vas deferens by excitatory (H₂ receptors) and inhibitory (H₁ receptors) receptors. Histamine was able to decrease the tonic response for noradrenaline-induced contractions with participation of H₁ receptors (testicular capsule) and H₃ receptors (vas deferens) followed by nitric oxide generation. At high concentration, histamine exerts contractile effects in both tissues. In the testicular capsule, the histamine-induced contractions were related to H₁ receptor activation followed by release of prostaglandins. In contrast, the contractile effects of histamine in the vas deferens were related to H₂ receptor activation followed by release of catecholamines from sympathetic nerve endings. Therefore, our results indicate that histamine induced several effects on the sympathetic neurotransmission of rat testicular capsule and vas deferens. These effects are dependent on the concentration used and with participation of multiple histamine receptors.     

Development of local connections in ferret somatosensory cortex

Ferrets have become recognized as a useful and interesting model for study of neocortical development. Because of their immaturity at birth, it is possible to study very early events in the ontogeny of the brain. We used living slices of ferret somatosensory cortex to study the formation and development of intrinsic elements within the neocortex. A small number of fixed, hemisected brains injected with 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) were also used. The slices were obtained from ferret kits aged postnatal day (P)1 to P62 and maintained in a chamber; each slice received injections of fluorescent-labeled dextrans. The injections were made at different ages in several distinct sites, which included the proliferative ventricular zone, the intervening white matter (or intermediate zone), and different sites of developing cortex, including the deeper cortical plate, which incorporated the subplate in young animals, and more superficial cortical sites, depending on the age of the animal. Several animals also received injections into the ventrobasal thalamus. Injections into young animals (P1–7) produced a dominant radial pattern that extended from the ventricular zone into the cortex. Injections into the ventricular zone labeled many cells that appeared morphologically like radial glia as well as presumptive neurons. Although the predominant pattern was radial, injections in the ventricular zone often produced tangentially oriented cells and horizontally arranged fibers at the outer edge of the proliferative zone. These cells and fibers may provide a substrate for tangential dispersion of neurons within the neocortex. More superficial injections within the slice labeled lines of cells that appeared to be stacked upon one another in a radial pile in the cortex; the cortical plate received very few lateral projections. Data obtained from more mature slices indicated that, although the overall pattern of staining remained radial, the precise character of the pattern changed to include more lateral spread into surrounding cortex, which eventually refined and developed into distinct patches by P28, when the overall cortical architecture appeared adult like. The data involving thalamocortical connections were more limited, but they indicated that the thalamus projects precisely to the somatosensory cortex in a point-to-point fashion from the earliest date studied (P0) and that the ventrobasal nucleus terminates upon the somatosensory cortex in a patchy manner during the early postnatal days of development. This study of the development of the somatosensory cortex confirms the ubiquitous nature of column-like connections throughout the neocortex and provides a novel view of the radial nature of early neocortical maturation. © Wiley-Liss, Inc.     

Dacarbazine alone or associated with melanoma-bearing cancer pain model induces painful hypersensitivity by TRPA1 activation in mice

Antineoplastic therapy has been associated with pain syndrome development characterized by acute and chronic pain. The chemotherapeutic agent dacarbazine, used mainly to treat metastatic melanoma, is reported to cause painful symptoms, compromising patient quality of life. Evidence has proposed that transient receptor potential ankyrin 1 (TRPA1) plays a critical role in chemotherapy-induced pain syndrome. Here, we investigated whether dacarbazine causes painful hypersensitivity in naive or melanoma-bearing mice and the involvement of TRPA1 in these models. Mouse dorsal root ganglion (DRG) neurons and human TRPA1-transfected HEK293 (hTRPA1-HEK293) cells were used to evaluate the TRPA1-mediated calcium response evoked by dacarbazine. Mechanical and cold allodynia were evaluated after acute or repeated dacarbazine administration in naive mice or after inoculation of B16-F10 melanoma cells in C57BL/6 mice. TRPA1 involvement was investigated by using pharmacological and genetic tools (selective antagonist or antisense oligonucleotide treatment and Trpa1 knockout mice). Dacarbazine directly activated TRPA1 in hTRPA1-HEK293 cells and mouse DRG neurons and appears to sensitize TRPA1 indirectly by generating oxidative stress products. Moreover, dacarbazine caused mechanical and cold allodynia in naive but not Trpa1 knockout mice. Also, dacarbazine-induced nociception was reduced by the pharmacological TRPA1 blockade (antagonism), antioxidants, and by ablation of TRPA1 expression. TRPA1 pharmacological blockade also reduced dacarbazine-induced nociception in a tumor-associated pain model. Thus, dacarbazine causes nociception by TRPA1 activation, indicating that this receptor may represent a pharmacological target for treating chemotherapy-induced pain syndrome in cancer patients submitted to antineoplastic treatment with dacarbazine.     

NI-RADS for head and neck cancer surveillance imaging: What,why, and how

The Neck Imaging Reporting and Data System (NI-RADS) was conceived in 2016 with the objective of standardizing assessment and reporting in surveillance imaging for patients with head and neck squamous cell carcinomas and their subsequent management. The goals are to simplify radiology reports while increasing the consistency and accuracy of the interpretation of cancer surveillance imaging; enable better communication among clinicians and between clinicians and patients; facilitate outcomes research; and ultimately improve patient survival, morbidity, and mortality. The objective of the current study was to provide the background as to why and how NI-RADS was conceived and what it entails in radiology reporting.     

Adjuvant Therapy With Sodium Alendronate for the Treatment of Experimental Periodontitis in Rats

Background: This study assesses the effects of topical sodium alendronate (SA) as an adjuvant to the mechanical treatment of ligature‐induced periodontitis in rats. Methods: Ninety animals were subjected to the induction of periodontitis via the installation of a ligature around the mandibular left first molar. After 7 days, the ligature was removed, and the animals were distributed into the following groups: 1) NT group (n = 30), no treatment; 2) SRP group (n = 30), scaling and root planing (SRP) and local irrigation with physiologic saline solution; and 3) SRP/SA group (n = 30), SRP and local irrigation with SA (10^?5 M). Ten animals from each group were euthanized at 7, 15, and 30 days after treatment. Histologic and histometric analyses were performed in the furcation region. The percentage of bone in the furcation (PBF) was measured. Immunohistochemical analyses for detecting the receptor activator of nuclear factor‐κB ligand (RANKL), osteoprotegerin (OPG), tartrate‐resistant acid phosphatase (TRAP), and activated caspase‐3 were performed at the furcation region. Results: Compared with the other groups, the SRP/SA group showed less local inflammation and better tissue reparation during the entire experiment. There was more PBF in the SRP/SA group than in the other groups at days 7 and 15. Stronger OPG immunolabeling and weaker RANKL immunolabeling were observed in the SRP/SA group at 15 and 30 days. There were fewer TRAP‐positive cells in the SRP/SA group than in the NT group at all of the time points. There was no difference in the number of activated caspase‐3‐positive osteocytes among groups and time points. Conclusion: It can be concluded that topical use of SA as an adjuvant to SRP is effective in the treatment of experimental periodontitis.