Congestive Hepatopathy Secondary to Right Ventricular Hypertrophy Related to Monocrotaline-Induced Pulmonary Arterial Hypertension.

Heart dysfunction and liver disease often coexist. Among the types of cardiohepatic syndrome, Type 2 is characterized by the chronic impairment of cardiac function, leading to chronic liver injury, referred to as congestive hepatopathy (CH). In this study, we aimed to establish a rat model of CH secondary to right ventricular hypertrophy (RVH) related to monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Fifty male Wistar rats were divided into four groups and randomly assigned to control and experimental groups. Three experimental groups were submitted to intraperitoneal MCT inoculation (60 mg/kg) and were under its effect for 15, 30 and 37 days. The animals were then sacrificed, obtaining cardiac and hepatic tissues for anatomopathological and morphometric analysis. At macroscopic examination, the livers in the MCT groups presented a nutmeg-like appearance. PAH produced marked RVH and dilatation in the MCT groups, characterized by a significant increase in right ventricular free wall thickness (RVFWT) and chamber area. At histological evaluation, centrilobular congestion was the earliest manifestation, with preservation of the hepatocytes. Centrilobular hemorrhagic necrosis was observed in the groups exposed to prolonged MCT. Sinusoidal dilatation was markedly increased in the MCT groups, quantified by the Sinusoidal Lumen Ratio (SLR). The Congestive Hepatic Fibrosis Score and the Centrilobular Fibrosis Ratio (CFR) were also significantly increased in the MCT30 group. Hepatic atrophy, steatosis, apoptotic bodies and, rarely, hydropic swelling were also observed. SLR correlated strongly with CFR and RVFWT, and CFR correlated moderately with RVFWT. Our rat model was able to cause CH, related to monocrotaline-induced PAH and RVH; it was feasible, reproducible, and safe.

Bone repair in craniofacial defects treated with different doses of alendronate: a histological, histomorphometric, and immunohistochemical study.

OBJECTIVE: The objective of the study is to evaluate bone repair in rats treated with different alendronate doses. MATHERIALS AND METHODS: Sixty female rats ovariectomized were randomly divided in three groups: group C (control group), group A1 (ALN/1 mg/kg), and A2 (ALN/ 3 mg/kg). Each animal received subcutaneous applications of sodium alendronate at a dose correspondent to group A1 or A2 three times a week, while the control group received 0.9% saline solution. After 4 weeks of application, a critical defect was created in the calvaria of animals of all groups. The defect was filled by particulate autogenous bone. The applications were maintained until euthanasia, which occurred 15 and 60 days after the surgical procedure. The pieces were sent for histological, histomorphometric and immunohistochemical analysis. The data were submitted to statistical analysis with significance level of 0.05. RESULTS: The descriptive histological analysis demonstrated an increase in bone neoformation in both groups treated with alendronate when compared to the control group. The histomorphometric analysis showed an increase in the amount of neoformed bone in A1 and A2 groups when compared to group C, both at 15 days (p = 0.0002) and at 60 days (p = 0.001). In the immunohistochemical analysis, it was possible to observe a difference in immunolabeling just for Mmp2 at the time of 60 days in A1 (p = 0.001) and A2 (p = 0.023) when compared to the control group. CONCLUSION: Systemic delivery of alendronate, regardless of the dose, increased the amount of bone neoformation. CLINICAL RELEVANCE: Prescription of sodium alendronate at 1 mg/kg for improvement of bone neoformation in bone graft procedures.

Large Anterior Oronasal Fistula Repair Using Pedicled Buccal Fat Pad and Fibroepithelial Tissue.

Oronasal fistula (ONF) is the most common complication after palatoplasty in patients with cleft lip and palate (CLP). When left untreated, it may negatively affect the quality of life, leading to development of other comorbidities. This study reports for the first time, the use of a portion of a hyperplasic tissue associated with pedicled buccal fat pad flap to repair a large anterior ONF in a 60-year-old man. The hyperplasic tissue may have developed due to the combination of a loose fitting upper denture and long-term use of dihydropyridine calcium channel blocker (amlodipine besylate). There is controversy in the literature about use of pedicled buccal fat pad flap in the anterior region. However, in this study, we report successful repair of a large anterior ONF using a portion of a fibroepithelial hyperplasic tissue associated with pedicled buccal fat pad flap.

Prolonged use of alendronate alters the biology of cranial repair in estrogen-deficient rats' associated simultaneous immunohistochemical expression of TGF-ß1+, α-ER+, and BMPR1B.

OBJECTIVES: TGF-ß1 is a cytokine that may induce both osteoneogenesis through Runx-2 or fibrosis via the transcription of α-smooth muscle actin (α-SMA). Because it has been previously known that alendronate increases the level of TGF-ß1 and that under the usual condition of bone metabolism the estrogen may prevent the fibrotic effect of TGF-ß1, the aim of this study was to evaluate if alendronate alters the cellular differentiation process post calvarial surgery in estrogen-deficient specimens. MATERIALS AND METHODS: A transosseous defect that was 5 mm in diameter was created on the calvarium of each of 32 female rats with previous ovarian-salpingo-oophorectomy. All defects were treated with autografts, and 16 rats received the administration of 1 mg/kg of alendronate three times a week until euthanasia on the 15th and 60th day post surgery. Histomorphometric and immunohistochemical analyses of the expression of TGF-ß1, estrogen receptor alpha nuclear (α-ER), α-SMA, BMPR1B, and Runx-2 were performed, and ELISA was used to measure the level of estrogen. RESULTS: All animals demonstrated low levels of estrogen post ovarian-salpingo-oophorectomy. The histological results demonstrated larger bone matrix deposition in specimens treated with alendronate on the 15th day post surgery. The result was associated with a higher co-expression of TGF-ß1, BMPR1B, and Runx-2 when compared with the control group. In addition, on the 60th day post surgery, the increase of bone matrix deposition from 15th to 60th day was discrete in specimens treated with alendronate compared with the control group. This result coincided with the intense simultaneous expression of TGF-ß1, α-ER, and α-SMA, whereas the expression of BMPR1B and Runx-2 decreased. CONCLUSION: The prolonged administration of alendronate altered the cranial repair in ovarian-salpingo-oophorectomized specimens due to the simultaneous occurrence of low estrogen and the presence of TGF-ß1+/α-ER+ inducing the presence of α-SMA+, whereas BMPR1B and Runx-2 were suppressed. CLINICAL RELEVANCE: The prolonged administration of alendronate alters osteoneogenesis and induces an unusual microenvironment in the bone that seems to imitate the physiological tissue damage that culminates in the loss of the functional layer of endometrium.

Use of Low-Dose Alendronate Improves Cranial Bone Repair and Is Associated With an Increase of Osteocalcin: An Experimental Study.

PURPOSE: The objective of the present study was to evaluate cranial bone repair and remodeling after systemic application of alendronate (ALN), using histologic analysis, histometric analysis, and immunohistochemistry (osteocalcin). MATERIALS AND METHODS: Female rabbits (n = 28) were randomly divided into 2 groups: control (C) and ALN treated (A). Group A received 3 systemic intraperitoneal injections of ALN weekly for 4 weeks, at a dose of 0.2 mg/kg. Group C received intraperitoneal injections of physiologic saline for the same period. After 4 weeks, all the rabbits underwent surgery to create 2 noncritical defects on the calvaria (5 mm in diameter). The groups were divided into 2 subgroups for sacrificing, at 15 and 60 postoperative days. After death, the analyses were performed. The data were also analyzed statistically. RESULTS: Histologic analysis of group C revealed healing in the dense connective tissue and trabecular bone, and the presence of compact bone with osteoblastic activity was noted in both 15- and 60-day subgroups. In group A, at 15 days, the presence of conjunctive tissue with osteoblastic activity and intense, compact, newly formed bone was observed. At 60 days, the created bone defect in group A showed a large amount of neoformed compact bone with a surface of dense modeled connective tissue and the presence of adipocytes and trabecular bone. The histometric analysis confirmed that a statistically significant difference was present between groups C and A when comparing the measured bone area and the area of connective tissue. Group A presented with a statistically significant larger amount of bone area in the 60-day subgroup than in the 15-day subgroup. The immunohistochemical analysis showed stronger immunostaining for osteocalcin in group A. CONCLUSIONS: Within the limits of the present study, our results have shown that the systemic application of ALN, at a dose of 0.2 mg/kg, increased the repair and remodeling of cranial bone.

Immunoexpression of IGF1, IGF2, and osteopontin in craniofacial bone repair associated with autogenous grafting in rat models treated with alendronate sodium.

OBJECTIVES: The aim of this study was to verify the likely influence of presurgical administration of low doses of alendronate sodium in craniofacial bone repair and correlate the histological frame found on reparative tissue to the immunohistochemical presence of IGF1, IGF2, and osteopontin (OP). MATERIALS AND METHODS: In total, 120 rats were randomly allocated into four groups: group C (control), group OA (autogenous bone), group B (bisphosphonates), and group OA-B (autogenous bone + bisphosphonates). Groups B and OA-B received alendronate sodium (ALN) 0.01 mg/kg subcutaneously on alternate days for 4 weeks. Groups C and OA received saline solution. Critical 5-mm defects were created in rat calvaria, which were filled with blood clot in groups C and B and with autogenous bone in groups OA and OA-B. The animals were euthanized at 15 or 30 days postoperatively. Histological analysis and immunohistochemistry of IGF1, IGF2, and OP proteins was performed. Immunohistochemistry evaluated the expression in cells and extracellular matrix. RESULTS: Groups C and B revealed healing predominantly characterized by connective tissue. In groups OA and OA-B, healing of connective tissue and neoformation of compact bone was observed. Expression of IGF1 an OP was present in all specimens. IGF1 expression in cells was more pronounced in groups OA and OA-B 15 days postoperatively. The expression of IGF2 was only observed in groups OA and OA-B, with greater intensity in group OA-B 30 days postoperatively. OP expression was only observed in cells and not in the extracellular matrix and was more pronounced in group OA 15 days postoperatively. CONCLUSIONS: The application of systemic ALN at a dose of 0.01 mg/kg did not improve cranial bone matrix deposition. Nevertheless, the expression of IGF1 and OP and a slight marking of IGF2 were observed especially in groups OA and OA-B in the wound healing process. Future studies should assess higher doses of ALN to verify its influence on bone repair. CLINICAL RELEVANCE: The systemic use of ALN 0.01 mg/kg on alternate days 4 weeks prior to surgery did not interfere with bone repair.

Would Be Prophylactic Administrations of Low Concentration of Alendronate an Alternative for Improving the Craniofacial Bone Repair? A Preliminary Study Focused in the Period of Cellular Differentiation and Tissue Organization.

BACKGROUND: Alendronate (ALN) is a nitrogen-bisphosphonate that may induce an anabolic effect on craniofacial bone repair when administrated in low doses. Based on this premise, this study analyzed the influence of prophylactic low doses of ALN on bone healing in defects created in rabbit mandible. METHODS: A 5 × 2-mm diameter deep defect was created in the calvaria of 28 rabbits. Fourteen of these rabbits received previously 50 µg/kg of 1% sodium ALN for 4 weeks, while the other rabbits received only 0.9% physiological saline solution (control). Animals were euthanized at 15 and 60 days postsurgery (n = 7), and the data were analyzed using histomorphometry and immunohistochemistry using the anti-CD34, bone morphogenetic protein -2 (BMP-2), and transforming growth factor (TGF)-ß1 antibodies. RESULTS: On the 15th day postsurgery, the specimens that received previous treatment with ALN demonstrated large vascular lumen and intense positivity to CD34 either concentrated in endothelium or cells spread among the reparative tissue. These results coincided with intense positivity for BMP-2+ cells and TGF-ß1 that was concentrated in both cells and perivascular area. In contrast, the control group revealed scarce cells that exhibited CD34, BMP-2+, and the TGF-ß1 was restricted for perivascular area on well-formed granulation tissue. These patterns of immunohistochemical result, especially found on the 15th day of analysis, seem to be responsible for the development of larger quantities of bone matrix in the specimens that receive ALN on the 60th day postsurgery. CONCLUSION: These preliminary results showed that the prophylactic administration of low doses of ALN might be an alternative to craniofacial bone craniofacial bone repair because it increases the immunopositivity for TGF-ß1 and consequently improves the CD34+ and BMP-2+ cells on reparative sites.

Effect of alendronate on the progression of periodontitis induced by Porphyromonas gingivalis and Fusobacterium nucleatum: a study in rats.

OBJECTIVE: The study aimed to investigate the effect of alendronate (ALN) on the inhibition of alveolar bone loss in experimental periodontitis in Wistar rats. MATERIALS AND METHODS: Periodontitis was induced by oral inoculation of Porphyromonas gingivalis with Fusobacterium nucleatum. The rats (n = 80) were randomized as follows: negative control (n = 10); positive control (n = 10); ALN groups: test 8 (n = 10), test 12 (n = 10), and test 16 (n = 10); and placebo groups: control 8 (n = 10), control 12 (n = 10), and control 16 (n = 10). Two milligrams per kilogram of ALN or placebo was administered twice weekly for 8, 12, and 16 weeks. Bone loss was determined by morphological and histological analyses. One independent, blinded examiner (ICC, 0.91) performed the measurements. The distance from the cement enamel junction to the alveolar bone crest of the second lower molar was measured: distal-vestibular (d), furca (f), mesial-vestibular (h), and area. Histometry was performed on the second contralateral molar. Sections (6 µm) were used to determine the furcation bone area (A-FB). The following statistical analyses were conducted: Mann-Whitney and Kruskal-Wallis. RESULTS: PC group developed periodontitis (p < 0.0001). Morphometric analysis determined that ALN was effective in T8 for linear measurements d, f, and h (p < 0.05). No significant differences occurred at test 8, test 12, and test 16. Analysis of A-FB revealed no significant differences between the ALN and placebo groups at 8 and 16 weeks (p > 0.05). ALN was effective against bone loss in relation to A-FB after 12 weeks (p < 0.0001). CONCLUSIONS: According to the methodology used, the results suggest that oral administration of ALN could influence alveolar bone loss in rats submitted to experimental periodontitis. CLINICAL RELEVANCE: ALN could be a potential therapeutic approach when associated with periodontal treatment.

Influence of Metal and Ceramic Abutments on the Stress Distribution Around Narrow Implants: A Photoelastic Stress Analysis.

PURPOSE: This study aimed to compare, through photoelastic analysis, the distribution of stresses around narrow implants with external hexagon (EH) and Morse taper (MT) connections, when single crowns made with metal and ceramic abutments were used. MATERIALS AND METHODS: Six photoelastic models were prepared, simulating the use of narrow EH and MT implants replacing a lateral incisor. These 2 groups received 3 different abutments: prefabricated metal abutments, customized metal abutments, and customized zirconia abutments. All crowns were identical and made with a leucite reinforced glass-ceramic. Vertical loads of 0 to 100 N were applied on the palatal surface of the crowns, and the photoelastic stress fringes developed in each model were captured in a high-definition video, and digital photographs were taken at 100 N. RESULTS: The abutment type and material influenced the stress distribution patterns around narrow implants with EH and MT connections. Stresses were generated mainly around the apical and lingual regions of the implants. CONCLUSIONS: For both connections, the prefabricated metal abutments presented better stress distribution around the implants when compared to customized metal and zirconia abutments because low stress levels were developed in smaller areas around the implants.

Tissue reaction of deproteinized bovine bone matrix grafting in ectopic site: histological study on sheep.

The aim of this paper was to evaluate through histological analysis of the tissue reaction of deproteinized bovine bone matrix (DBBM) when inserted into the site of intramuscular ectopic sheep. In this study, 16 sheep received 3 groups and these were divided into 2 experimental times: Group 1-sham group, Group 2-particulate autogenous bone and Group 3-DBBM granules. All animals underwent surgical procedures for insertion of materials in an ectopic site (muscles of the lower back and after 3 and 6 months postoperatively, the samples were evaluated by histological analysis. The results indicated that the Sham group showed dense collagen fibers and thin, characterizing fibrosis at 3 and 6 months. In the autograft group there was a significant amount of collagen deposition and decreased inflammation at 6 months postoperatively. Group of DBBM, it was noted the presence of dense connective tissue and surrounding remaining particles was observed the formation of with osteoid characteristic tissue. The DBBM demonstrated biocompatibility, osteoconductivity and small osteogenesis capacity on ectopic site.

Amoxicillin diminishes the thickness of the enamel matrix that is deposited during the secretory stage in rats.

BACKGROUND: The use of amoxicillin during early childhood has been associated with molar incisor hypomineralization. AIM: The objective of this study was to determine whether the use of amoxicillin interferes with enamel development, during secretion and early mineralization stages. DESIGN: Fifteen pregnant rats were randomly assigned to three groups that received physiological solution (sham group), 100 mg/kg/day amoxicillin (A100G), and 500 mg/kg/day amoxicillin (A500G). After birth, the pups in each group received the same treatment until post-natal day 7 or 12. The upper first molars were analyzed histomorphometrical and immunostaining with amelogenin on day 7, and MMP-20 on day 12 was performed using a semiquantitative method (H-score). RESULTS: At 7 days, several vacuolar structures were observed in the ameloblasts in the A100G and A500G groups. A significant reduction of the enamel thickness (P < 0.001) was found in amoxicillin-treated rats compared with the sham group. Significant differences were not observed in enamel thickness (P > 0.05) between the groups of 12-day-old rats. Moreover, significant differences were not observed in the number of amelogenin- and MMP-20-immunolabeled ameloblasts (P > 0.05) between groups. CONCLUSION: The present results suggest that amoxicillin interferes with the initial stages of amelogenesis by causing structural changes in the ameloblasts and a reduction of the enamel matrix.

Sclerotherapy and cryotherapy in the management of oral vascular lesions: a series of 10 cases.

Vascular anomalies such as hemangiomas or vascular malformations can produce negative esthetic effects in the maxillofacial region. These negative effects are the main complaints of patients. The clinical therapeutic efficacy of cryotherapy and sclerotherapy in the treatment of these lesions was evaluated in 10 patients who were clinically diagnosed with vascular lesions. Lesions were submitted to either cryotherapy or sclerotherapy, and follow-up showed that cryotherapy and sclerotherapy both were clinically effective in treating oral vascular lesions. Cryotherapy is an easy to perform method that requires only 1 session, but the high cost of the equipment is a limiting factor. Sclerotherapy is a noninvasive treatment widely accepted by patients, but more than 1 session is required.

Influence of Prior Cervical Enlargement on Apical Cleaning Using Single File.

The goal of this study was to compare the apical cleaning capabilities of single files from 3 different rotary systems in the presence or absence of prior cervical preparation based on a histological analysis. A total of 84 human single-rooted mandibular permanent incisors were divided into 6 groups (14 canals each). Cleaning and shaping was performed under the following protocols: Group I, F2 ProTaper at working length; Group II, SX ProTaper and F2 ProTaper; Group III, size 25, .06 taper Mtwo at working length; Group IV, SX ProTaper and size 25, .06 taper Mtwo; Group V, size 25, .06 taper BR3 BioRace at working length; and Group VI, SX ProTaper and size 25, .06 taper BR3 BioRace. After cleaning and shaping, the root canals were evaluated by histological analysis. The percentage of remaining debris was evaluated using a cross-hatched grid superimposed over each image. Data were assessed using the Shapiro-Wilk and ANOVA tests. Statistically significant differences were observed between groups (p =0.0001) with respect to amount of remaining debris; use of SX in conjunction with F2 ProTaper yielded a significantly lower mean percentage of debris. It was concluded that cleaning ability improves when root canal preparation with F2 ProTaper is complemented by prior cervical enlargement.

Nonprocessed adipose tissue graft in the treatment of peri-implant osseous defects in the rabbit's tibiae: a pilot study.

We hypothesized that a new technique using nonprocessed adipose tissue could regenerate bone around dental implants. Eighteen rabbits received 1 implant per tibia surrounded by a surgically created osseous defect. The defects were assigned for treatment into 3 groups: C, AT, and AB. The percentages of bone-to-implant contact were 17.64% ± 16.22% (AB), 3.54% ± 7.08% (AT), and 12.71% ± 10.11% (C) (ρ = 0.25). The use of adipose tissue around surgically created peri-implant osseous defects interferes with bone formation.

Teledentistry: distant diagnosis of oral disease using e-mails.

OBJECTIVE: The purpose of this study was to evaluate the applicability of telediagnosis in oral medicine, through the transmission of clinical digital images by e-mail. SUBJECTS AND METHODS: The sample included 60 consecutive patients who sought oral medicine services at the Federal University of Paraná, in the state of Paraná, located in southern Brazil. The clinical history and oral lesion images were recorded using clinical electronic charts and a digital camera, respectively, and sent by e-mail to two oral medicine consultants. The consultants provided a maximum of two clinical hypotheses for each case, which were compared with biopsy results that served as the gold standard. RESULTS: In 31 of the 60 cases (51.7%), both consultants made the correct diagnosis; in 17 cases (28.3%), only one consultant made the correct diagnosis; and in 12 cases (20%), neither consultant made the correct diagnosis. Therefore, in 80% of cases, at least one consultant provided the correct diagnosis. The agreement between the first consultant and the gold standard was substantial (κ=0.669), and the agreement between the second consultant and the gold standard was fair (κ=0.574). CONCLUSIONS: The use of information technology can increase the accuracy of consultations in oral medicine. As expected, the participation of two remote experts increased the possibility of correct diagnosis.

Fragmented adipose tissue transplanted to craniofacial deformities induces bone repair associated with immunoexpression of adiponectin and parathyroid hormone 1-receptor.

Objective : This study analyzed the influence of autogenous white adipose tissue on bone matrix development in critical-size defects created in rabbit calvaria. Materials and methods : A 15-mm-diameter defect was created in the calvaria of 42 rabbits. Twenty-one rabbits were treated with 86 mm(3) of immediate transplant of fragmented white subcutaneous adipose tissue (WSAT); the others constituted the control group (sham). The animals were euthanized at 7, 15, and 40 days postsurgery (n = 7), and the histological data were analyzed by histomorphometry and immunohistochemistry using the anti-adiponectin and parathyroid hormone 1-receptor (PTH1R) antibodies. Results : The calvariae treated with fragmented WSAT demonstrated significant bone formation. These results coincided with the significant presence of immunopositivity to adiponectin and PTH1R in loci, which in turn coincided with the increase in bonelike matrix deposited both in fat tissue stroma and adipocytes' cytoplasm. In contrast, the control group revealed a small amount of bone-matrix deposition and presented scarce PTH1R expression and a lack of immunostain for adiponectin. Conclusion : These results indicate that transplant of fragmented white subcutaneous adipose tissue may be an alternative to treatment of craniofacial bone deformities because adipose tissue suffers from osseous metaplasia and exhibits immunoexpression of the adiponectin and PTH1R, which are proteins associated with bone metabolism.

Fragmented adipose tissue graft for bone healing: histological and histometric study in rabbits' calvaria.

OBJECTIVE: The adipose tissue represents an important reservoir of stem cells. There are few studies in the literature with which to histologically evaluate whether or not the adipose tissue graft is really a safe option to achieve bone repair. This study histologically analyzed the effect of fragmented autogenous adipose tissue grafts on bone healing in surgically created, critical-size defects (CSD) in a rabbit's calvaria. STUDY DESIGN: Forty-two New Zealand rabbits were used in this study. CSD that were 15 mm in diameter were created in the calvarium of each animal. The defects were randomly divided into two groups: in Group C (control), the defect was filled only by a blood clot and, in Group FAT (i.e., fragmented adipose tissue), the defect was filled with fragmented autogenous adipose tissue grafts. The groups were divided into subgroups (n = 7) for euthanasia at 7, 15, and 40 days after the procedure had been conducted. Histologic and histometric analyses were performed. Data were statistically analysed with ANOVA and Tukey's tests (p < 0.05). RESULTS: The amount of bone formation did not show statistically significant differences seven days after the operation, which indicates that the groups had similar amounts of mineral deposition in the earlier period of the repair. Conversely, a significant of amount of bone matrix deposition was identified in the FAT group at 15 and 40 days following the operation, both on the border and in the body of the defect. Such an outcome was not found in the control group. CONCLUSION: In this study, an autologous adipose tissue graft may be considered as likely biomaterial for bone regeneration, since it positively affected the amount of bone formation in surgically created CSD in the rabbits' calvaria 40 days after the procedure had been performed. Further investigations with a longer time evaluation are warranted to determine the effectiveness of autologous adipose tissue graft in the bone healing.

Bioactive glass and connective tissue graft used to treat intrabony periodontal defects.

Different techniques and materials can be used to treat intrabony periodontal defects caused by periodontal diseases. This case report presents an intrabony periodontal defect with bioactive glass and connective tissue graft used as a barrier. Probing depth and clinical attachment gain were reduced at 6 and 12 months post-treatment.

Prolong intermittent injection of human parathyroid hormone in rats modulates the expression of several proteins in the neuropil of the cerebellar cortex.

INTRODUCTION: The intermittent use of recombinant human parathyroid hormone (iPTH) alters calcium metabolism and induces osteogenesis in experimental models. However, the real effects of iPTH in excitable cells and neurons that require membrane receptors to undergo membrane depolarization/repolarization (Na+K+ATPase) to generate ATP, voltage-gated calcium channel (calcium-IP3R-calponin) as well as GABAergic (GABAA) signaling remains unclear. OBJECTIVES: In this study, the expression of IP3R, Na+K+-ATPase, GABAA and calmodulin proteins were evaluated in histological sections of the cerebellum of rats following prolonged injection of iPTH. METHODS: Twenty Wistar rats were used in this study and randomly assigned as either or control group. The test group were subcutaneously injected with 20 µg/kg of iPTH, 3×/week for 8 weeks, while the control group received 1 ml/kg of 0.9% saline solution. The rats were euthanized on the 60th day after the first administration, and their cerebellar vermis was removed and submitted to histological and immunohistochemical evaluation for detection of IP3R, Na+K+-ATPase, GABAA and calmodulin proteins. The expression of proteins was evaluated in the areas corresponding to the Purkinje cells as well as in neuropil of molecular layer of cerebellum. All results were transformed into a percentage for each area analyzed to verify significance between groups. RESULTS: Rats that received iPTH demonstrated significant reduction of IP3R, calmodulin and GABAA in Purkinje cells and neuropil of molecular layer while the expression of Na+K+-ATPase was similar. CONCLUSION: It was concluded that iPTH decreased the expression of IP3R and calmodulin while it did not alter the expression of Na+K+-ATPase. These changes insinuate the ionic activity of calcium and sodium/potassium. Yet, the iPTH alters GABAergic signaling in Purkinje cells, suggesting neurotransmission activity changes in the cerebellum.