Crosslinked Collagen-Hyaluronic Acid Scaffold Enhances Interleukin-10 Under Co-Culture of Macrophages And Adipose-Derived Stem Cells.

The skin, the human body's largest organ, possesses a protective barrier that renders it susceptible to various injuries, including burns. Following burn trauma, the inflammatory process triggers both innate and adaptive immune responses, leading to the polarization of macrophages into two distinct phenotypes: the pro-inflammatory M1 and the anti-inflammatory M2. This dual response sets the stage for wound healing and subsequent tissue regeneration. Contributing to this transition from M1 to M2 polarization are human adipose-derived stem cells (ASCs), which employ paracrine signaling and inflammation suppression to enhance the remodeling phase. ASCs, when combined with biocompatible polymers, can be integrated into functional scaffolds. This study introduces an 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide-crosslinked (EDC-crosslinked) collagen-hyaluronic acid (Col-HA) scaffold assembled with ASCs, designed as a natural biomaterial device to modulate macrophage behavior in vitro under co-culture conditions. This innovation aims to improve wound healing processes. The EDC-crosslinked Col-HA scaffold favored the release of anti-inflammatory cytokines by ASCs, which indicated the M2 prevalence. In tissue engineering, a critical objective lies in the development of functional biomaterials capable of guiding specific tissue responses, notably the control of inflammatory processes. Thus, this research not only presents original findings but also points toward a promising avenue within regenerative medicine.

Cancer Inhibition and In Vivo Osteointegration and Compatibility of Gallium-Doped Bioactive Glasses for Osteosarcoma Applications.

Traditional osteosarcoma therapies tend to focus solely on eradicating residual cancer cells and often fail to promote local bone regeneration and even inhibit it due to lack of precise control over target cells, i.e., the treatment affects both normal and cancer cells. Typically, multistep procedures are required for optimal efficacy. Here, we found that a silica-based bioactive material containing 3 mol % gallium oxide selectively kills human osteosarcoma cells and presents excellent in vivo osteointegration, while showing no local or systemic toxicity. Cell culture media conditioned with the proposed material was able to kill 41% of osteosarcoma cells, and no significant deleterious effect on normal human osteoblasts was observed. In addition, rats treated with the gallium-doped material showed excellent material-bone integration with no sign of local toxicity or implant rejection. Systemic biocompatibility investigation did not indicate any sign of toxicity, with no presence of fibrosis or cellular infiltrate in the histological microstructure of the liver and kidneys after 56 days of observation. Taken together, these results show that synergistic bone regeneration and targeted cancer therapy can be combined, paving the way toward new bone cancer treatment approaches.

Effects of low-intensity pulsed ultrasound exposure on rats tibia periosteum.

The periosteum is a rich source of osteoprogenitor cells and periosteal grafts can be used as an alternative method to replace bone grafts. The low-intensity pulsed ultrasound (LIPUS) has often been used as a noninvasive method to stimulate osteogenesis and reduce the fracture healing time. The aim of this study was to evaluate the effects of the ultrasound exposure on the rat tibia periosteum. Group I (7 animals) received LIPUS therapy on the left tibia for 7 days and group II (7 animals) on the left tibia for 14 days. After euthanasia, the tibias were processed. Number of periosteal cells and vessels and thickness of the periosteum were analyzed. The number of periosteal cells was higher in stimulated periosteum compared to controls at 7 and 14 days, but the number of vessels and the thickness only were higher in the group stimulated at 14 days. Furthermore, the ultrasound treatment for 14 days was more effective than 7 days. The ultrasound stimulation of the periosteum prior to grafting procedure can be advantageous, since it increases periosteal activity, and LIPUS may be an alternative method for stimulating the periosteum when the use of periosteal grafts in bone repair is needed.

Comprehensive in vitro and in vivo studies of novel melt-derived Nb-substituted 45S5 bioglass reveal its enhanced bioactive properties for bone healing.

The present work presents and discusses the results of a comprehensive study on the bioactive properties of Nb-substituted silicate glass derived from 45S5 bioglass. In vitro and in vivo experiments were performed. We undertook three different types of in vitro analyses: (i) investigation of the kinetics of chemical reactivity and the bioactivity of Nb-substituted glass in simulated body fluid (SBF) by 31P MASNMR spectroscopy, (ii) determination of ionic leaching profiles in buffered solution by inductively coupled plasma optical emission spectrometry (ICP-OES), and (iii) assessment of the compatibility and osteogenic differentiation of human embryonic stem cells (hESCs) treated with dissolution products of different compositions of Nb-substituted glass. The results revealed that Nb-substituted glass is not toxic to hESCs. Moreover, adding up to 1.3 mol% of Nb2O5 to 45S5 bioglass significantly enhanced its osteogenic capacity. For the in vivo experiments, trial glass rods were implanted into circular defects in rat tibia in order to evaluate their biocompatibility and bioactivity. Results showed all Nb-containing glass was biocompatible and that the addition of 1.3 mol% of Nb2O5, replacing phosphorous, increases the osteostimulation of bioglass. Therefore, these results support the assertion that Nb-substituted glass is suitable for biomedical applications.

Addition of Wollastonite Fibers to Calcium Phosphate Cement Increases Cell Viability and Stimulates Differentiation of Osteoblast-Like Cells.

Calcium phosphate cement (CPC) that is based on α-tricalcium phosphate (α-TCP) is considered desirable for bone tissue engineering because of its relatively rapid degradation properties. However, such cement is relatively weak, restricting its use to areas of low mechanical stress. Wollastonite fibers (WF) have been used to improve the mechanical strength of biomaterials. However, the biological properties of WF remain poorly understood. Here, we tested the response of osteoblast-like cells to being cultured on CPC reinforced with 5% of WF (CPC-WF). We found that both types of cement studied achieved an ion balance for calcium and phosphate after 3 days of immersion in culture medium and this allowed subsequent long-term cell culture. CPC-WF increased cell viability and stimulated cell differentiation, compared to nonreinforced CPC. We hypothesize that late silicon release by CPC-WF induces increased cell proliferation and differentiation. Based on our findings, we propose that CPC-WF is a promising material for bone tissue engineering applications.

Metabolic and structural bone disturbances induced by hyperlipidic diet in mice treated with simvastatin.

Simvastatin can modulate lipid and bone metabolism. However, information related to the interaction between diet and simvastatin on bone structure and biomechanics is scarce. Thus, this study evaluated the effects of simvastatin on femoral biomechanics and cortical/trabecular bone structure in wild-type mice nourished with a hyperlipidic diet. Three-month-old male wild-type mice (C57BL6 strain) were divided into four groups: (1) group W, nourished with a standard diet; (2) group WH, fed a hyperlipidic diet; (3) group WS, nourished with a standard diet plus oral simvastatin (20 mg/kg/day); and (4) group WHS, fed a hyperlipidic diet plus oral simvastatin (20 mg/kg/day). All animals received only their specific diet and water for 60 days. Blood samples were collected for the analysis of calcium, triglycerides, total cholesterol (TC) and fraction serum levels. Diet manipulation was able to induce a dyslipidaemic status in mice, characterized by triglyceride and TC rise in WH animals. Simvastatin prevented hypercholesterolaemia and reduced TC and LDL serum levels, but did not prevent hypertriglyceridaemia and HDL serum levels in the WHS group. In the WH mice the hyperlipidaemia was associated with reduction in trabecular bone thickness, femur structural and material property alterations. Simvastatin prevented these morphological alterations and minimized femur biomechanical changes in WHS mice. Taken together, the results indicated that the hyperlipidic diet intake acts as a risk factor for bone integrity, generating bones with reduced resistance and more susceptible to fractures, an effect attenuated by simvastatin that is potentially related to the modulatory action of this drug on lipid and bone metabolism.

Mechanical and morphological aspects of the calcaneal tendon of mdx mice at 21 days of age.

A relationship between compromised muscles and other tissues has been demonstrated in mdx mouse, an animal model studied for understanding of Duchenne muscular dystrophy. The hypothesis is that changes in the calcaneal tendon of mdx mice occur previous to the onset of rigorous and most marked episodes of muscle degeneration, which start suddenly after 21 days of life. Thus, this study aimed to identify possible alterations in the calcaneal tendon of mdx mouse at 21 days of age. Control and mdx tendons were submitted to mechanical tensile testing, quantification of hydroxyproline, and staining with toluidine blue and picrosirius red. Hydroxyproline content was similar between mdx and control groups. The control tendon presented higher mechanical strength (load, stress, and elastic modulus) and its morphological analysis showed a larger number of round fibroblasts, nuclei with well-decondensed chromatin, and slightly metachromatic well-stained cytoplasmic material, different from that observed in mdx tendons. The results suggest that the absence of dystrophin in mdx mouse can provoke directly or indirectly alterations in the mechanical properties and morphology of the calcaneal tendon.

Efeito da dexametasona e do cetoprofeno na osteogênese e na resistência óssea em ratos / Effect of dexamethasone and ketoprofen on osteogenesis and bone resistance in rats

O presente estudo teve como objetivo avaliar o efeito do cetoprofeno e da dexametasona na osteogênese ao redor de implante de hidroxiapatita densa (HAD) na tíbia, no osso parietal, e na resistência óssea. Utilizaram-se 15 ratos Wistar, pesando 250±30 g, com 50 dias de idade. Após a anestesia com quetamina/xilazina IM, produziu-se no osso parietal e na epífise proximal da tíbia uma cavidade de 3 mm, sendo implantada a HAD. Após a cirurgia os animais foram divididos em três grupos (n=5): controle (CT), anti-inflamatório não esteroidal (AINES) e anti-inflamatório esteroidal (AIES). O grupo AINES foi submetido ao tratamento com cetoprofeno na dose de 12 mg/Kg/dia, o AIES recebeu doses de 0,10 mg/kg/dia de dexametasona o grupo CT recebeu solução fisiológica 0,9% (SF) por via subcutânea durante 30 dias. Todos os grupos receberam a mesma dieta sólida e água ad libitum. Após 30 dias de experimento os animais sofreram eutanásia, os fêmures coletados, para teste mecânico, e os locais do implante das tíbias e o osso parietal, para análise histomorfométrica. Os grupos AINES e AIES apresentaram menor volume de osso neoformado na falha óssea e ao redor do implante de HAD , como também, menor força máxima para a ruptura completa dos fêmures, quando comparados com o grupo CT. O uso do cetoprofeno e a dexametasona interferiram na osteogênese ao redor do implante de HAD e no osso parietal, diminuindo a resistência óssea principalmente pela inibição da COX2 e diminuição das prostaglandinas, comprometendo a estabilidade e manutenção do implante.

This study aimed at evaluating the effect of ketoprofen (NSAID) and dexamethasone (SAID) on osteogenesis around a dense hydroxyapatite (DHA) implant in the tibia and parietal bone, and on the bone resistance. Fifteen fifty-day-old Wistar rats weighing on average 250±30 g were used. The animals were separated into three groups (n=5): control (CT); non-steroidal anti-inflammatoryl (NSAID); and steroidal anti-inflammatory (SAID). After anesthesia with IM ketamine/xylazine, a 3 mm cavity was made in the left parietal bone and in the proximal epiphysis of the left tibia. A DHA bioceramic was implanted in the tibia. The animals were treated subcutaneously during 30 days as follows: NSAID group: ketoprofen at the dose of 12/Kg/day; SAID group: dexamethasone, 0,10 mg/kg/day. The CT group received saline through the same route. All the animals received the same solid diet and water ad libitum. After 30 days of experiment, the animals wereeuthanized, and their femurs collected for the mechanical test, while their tibia and parietal sites were prepared for the histomorphometrical analysis. Microscopically, the SAID and NSAID groups showed a lower volume of neoformed bone. In addition, the NSAID and SAID group femurs required lower maximum force for complete rupture when compared with the CT group. It was concluded that ketoprofen and dexamethasone interfered with osteogenesis and decreased bone resistance by altering the bone tissue metabolism, mainly by inhibiting the COX-2 and decreasing prostaglandins. Therefore, the use of ketoprofen and dexamethasone after bone surgeries can compromise the stability and maintenance of implants.

Effect of hyperlipidemia on femoral biomechanics and morphology in low-density lipoprotein receptor gene knockout mice.

The objective of this study was to evaluate the effect of hyperlipidemia on the biomechanical and morphological properties of the femur of low-density lipoprotein receptor gene knockout mice (LDLr-/-) mice. Ten wild-type mice (C57BL6) and 10 LDLr-/- mice generated on a C57BL6 background were used. Male 3-month-old animals were divided into four groups (n = 5): group W (wild type) and group L (LDLr-/-) receiving low-fat commercial ration, and group WH (wild type) and group LH (LDLr-/-) receiving a high-fat diet. After 60 days, blood samples were collected for laboratory analysis of calcium, triglycerides, and cholesterol. The femur was excised for mechanical testing and morphometric analysis. LDLr-/- mice receiving the high-fat diet presented more marked alterations in the mechanical and morphological properties of femoral cortical and trabecular bone. Changes in the plasma levels of calcium, triglycerides, cholesterol, and fractions were also more pronounced in this group. The present results demonstrate that hyperlipidemia causes alterations in the structure and mechanical properties of the femur of LDLr-/- mice. These effects were more pronounced when associated with a high-fat diet.

Spontaneous healing capacity of calvarial bone defects in mdx mice.

The mdx mouse is an experimental model widely used for the study of Duchenne muscular dystrophy, which is characterized by the lack of dystrophin and cycles of muscle degeneration/regeneration. Studies demonstrated elevated levels of growth factors and accelerated skin wound repair in these animals. We therefore raised the hypothesis that the bone repair process might also be altered in these animals. Thus, the objective of this study was to evaluate the spontaneous healing of calvarial defects in mdx mice by histomorphometric analysis. Animals (45 days old) were divided into mdx and control groups. A defect measuring 2 mm in diameter was produced surgically in the right parietal bone of each animal. The animals were sacrificed 15, 30, and 60 days after surgery, and the skulls were processed by routine histological procedures. No difference in the volume of new bone inside the defect was observed between the two groups at any of the three postoperative time points. There was also no difference between the different periods of healing when each group was analyzed separately. The lower quality of femoral and calvarial bone in mdx mice reported in previous studies and the similar bone regeneration rates seen in two groups suggest that the healing capacity of calvarial defects was more expressive in mdx mice than in control animals. An increase in the amount of osteogenic factors released by damaged myofibers may have favored osteogenesis during bone defect healing in mdx mice.

Bone tissue and muscle dystrophin deficiency in mdx mice.

Duchenne muscular dystrophy is a neuromuscular disease caused by the lack of dystrophin that affects skeletal muscles, causing degeneration of muscle fibers and replacing them with fibrous and adipose tissue, events that gradually lead to functional loss. Patients with Duchenne muscular dystrophy have shown that bones become more fragile with age and with advancement of the disease. Muscle weakness and reduced mobility have been suggested to be the factors that promote bone deterioration. However, it seems that this does not occur in mdx mice. It has been identified in mdx mice the existence of a factor related or not to the lack of dystrophin that also participates in the impairment of bone quality. Mdx mice also exhibit muscle degeneration, but unlike human, it is compensated by muscle regeneration. In consequence, there is an increase in the muscle mass, but not necessarily of muscle contractile strength. The accommodation of this increased muscle mass promotes bone formation at specific sites, such as at tendo-osseous junctions. In addition, the inflammatory response to muscle injury may be responsible for the increase in angiogenesis and regeneration observed in mdx mice, inducing the release of cytokines and chemokines that play an important role in the recruitment of leukocytes and macrophages. Then, mdx mice may possess compensatory mechanisms in bone in response to a genetic defect.

Mechanical, biochemical and morphometric alterations in the femur of mdx mice.

The bone tissue abnormalities observed in patients with Duchenne muscular dystrophy are frequently attributed to muscle weakness. In this condition, bones receive fewer mechanical stimuli, compromising the process of bone modeling. In the present study we hypothesize that other factors inherent to the disease might be associated with bone tissue impairment, irrespective of the presence of muscle impairment. Mdx mice lack dystrophin and present cycles of muscle degeneration/regeneration that become more intense in the third week of life. As observed in humans with muscular dystrophy, bone tissue abnormalities were found in mdx mice during more intense muscle degeneration due to age. Under these circumstances, muscle deficit is probably one of the factors promoting these changes. To test our hypothesis, we investigated the changes that occur in the femur of mdx mice at 21 days of age when muscle damage is still not significant. The mechanical (structural and material) and biochemical properties and morphometric characteristics of the femur of mdx and control animals were evaluated. The results demonstrated a lower strength, stiffness and energy absorption capacity in mdx femurs. Higher values for structural (load and stiffness) and material (stress, elastic modulus and toughness) properties were observed in the control group. Mdx femurs were shorter and were characterized by a smaller cortical area and thickness and a smaller area of epiphyseal trabecular bone. The hydroxyproline content was similar in the two groups, but there was a significant difference in the Ca/P ratios. Thermogravimetry showed a higher mineral matrix content in cortical bone of control animals. In conclusion, femurs of mdx mice presented impaired mechanical and biochemical properties as well as changes in collagen organization in the extracellular matrix. Thus, mdx mice developed femoral osteopenia even in the absence of significant muscle fiber degeneration. This weakness of the mdx femur is probably due to genetic factors that are directly or indirectly related to dystrophin deficiency.

Efeitos do fenobarbital sobre o reparo e a biomecânica de ossos em ratos Wi star / Effects of phenobarbital on bone repair and biomechanics in rats

OBJETIVO: Avaliar os efeitos morfológicos do tratamento com fenobarbital, sobre a neoformação óssea e sobre a biomecânica óssea do osso de ratos Wistar. MÉTODOS: Foram utilizados dez ratos divididos em dois grupos: controle (CT) e fenobarbital (FE). O grupo FE recebeu doses diárias de fenobarbital 0,035 ml/kg via intramuscular, por 60 dias. O grupo CT recebeu a mesma dose e via de administração de solução fisiológica 0,9 por cento. Após 30 dias, foi realizada uma falha óssea no osso parietal e implantada a hidroxiapatita porosa (HAP) em cavidades nas tíbias. Após as cirurgias, manteve os respectivos protocolos até completar 60 dias e serem eutanasiados, sendo os ossos coletados. RESULTADOS: O volume de osso formado ao redor HAP na falha parietal e os achados biomecânicos foram menores nos animais do grupo FE em relação ao CT. CONCLUSÃO: O uso prolongado do fenobarbital interfere no reparo ósseo após lesões, diminui a osseointegração de implantes de HAP e torna os ossos menos resistentes.

OBJECTIVE: To evaluate the morphological effects of phenobarbital treatment on new bone formation and on bone marrow biomechanics in Wistar rats. METHODS: We used ten rats that were divided into two groups: control (CT) and phenobarbital (FE). The FE group received daily doses of phenobarbital 0.035 ml / kg intramuscularly for 60 days. The CT group received the same dose and route of administration of 0.9 percent saline solution. After 30 days, we introduced a bone defect in the parietal bone and implanted porous hydroxyapatite (HAP) in cavities in the tibia. After surgery, we continued the protocols until the end of 60 days when the rats were euthanized, and the bones were collected. RESULTS: The volume of bone formed around HAP in parietal defect and biomechanical findings were lower in animals receiving FE compared to CT. CONCLUSION: Prolonged use of phenobarbital interferes with bone repair after injury, decreasing the osseointegration of HAP implants and making bones less resistant.

OBJETIVO: Evaluar los efectos morfológicos del tratamiento con fenobarbital, sobre la neoformación ósea y sobre la biomecánica ósea del hueso de ratas Wistar. MÉTODOS: Fueron utilizadas diez ratas divididas en dos grupos: control (CT) y fenobarbital (FE). El grupo FE recibió dosis diarias de fenobarbital 0,035 ml/kg vía intramuscular, por 60 días. El grupo CT recibió la misma dosis y vía de administración de solución fisiológica 0,9 por ciento. Después de 30 días, se realizó una falla ósea en el hueso parietal e implantó la hidroxiapatita porosa (HAP) en cavidades en las tibias. Después de las cirugías, se mantuvo los respectivos protocolos hasta completar 60 días y de ser eutanasiados, siendo recolectados los huesos. RESULTADOS: El volumen de hueso formado alrededor HAP en la falla parietal y los hallazgos biomecánicos fueron menores en los animales del grupo FE en relación al CT. CONCLUSIÓN: El uso prolongado del fenobarbital interfiere en la reparación ósea después de lesiones, disminuye la óseointegración de implantes de HAP y vuelve a los huesos menos resistentes.

Osteointegration of poly(L: -lactic acid)PLLA and poly(L: -lactic acid)PLLA/poly(ethylene oxide)PEO implants in rat tibiae.

Natural or synthetic materials may be used to aid tissue repair of fracture or pathologies where there has been a loss of bone mass. Polymeric materials have been widely studied, aiming at their use in orthopaedics and aesthetic plastic surgery. Polymeric biodegradable blends formed from two or more kinds of polymers could present faster degradation rate than homopolymers. The purpose of this work was to compare the biological response of two biomaterials: poly(L: -lactic acid)PLLA and poly(L: -lactic acid)PLLA/poly(ethylene oxide)PEO blend. Forty four-week-old rats were divided into two groups of 20 animals, of which one group received PLLA and the other PLLA/PEO implants. In each of the animals, one of the biomaterials was implanted in the proximal epiphysis of the right tibia. Each group was divided into subgroups of 5 animals, and sacrificed 2, 4, 8 and 16 weeks after surgery, respectively. Samples were then processed for analysis by light microscopy. Newly formed bone was found around both PLLA and PLLA/PEO implants. PLLA/PEO blends had a porous morphology after immersion in a buffer solution and in vivo implantation. The proportion 50/50 PLLA/PEO blend was adequate to promote this porous morphology, which resulted in gradual bone tissue growth into the implant.

Repair of cranial bone defects with calcium phosphate ceramic implant or autogenous bone graft.

Autogenous bone grafts have frequently been used in the treatment of bone defects; however, this procedure can cause clinical complications after surgery. Besides, the amount of available bone is sometimes insufficient. Therefore, synthetic biomaterials have been researched as an alternative to autogenous bone graft implants. The objective of this study was to evaluate the repair of bone defects treated with compact autogenous bone graft or porous calcium phosphate ceramics. Three defects 3 mm in diameter were produced in the skull of 21 rats. One the defects was produced in the frontal bone, which remained empty, while the others were produced in the right and left parietal bones, which were filled respectively with ceramics and autogenous bone graft. The animals were sacrificed 1, 2, 4, and 24 weeks after surgery and analyzed by light microscopy and radiography. In the twenty-fourth week, the defects filled with autogenous bone graft and ceramics had similar volumes of newly formed bone tissue. The ceramics offered favorable conditions to bone tissue growth. Thus, we concluded that the calcium phosphate ceramic implant proved to be effective in repairing defects produced in the skull of rats.

Morphological alterations in the epithelium of the oral mucosa of rats (Rattus norvegicus) submitted to long-term systemic nicotine treatment.

Smoking is considered to be the most albeit preventable cause of diseases and premature deaths in the history of mankind. The local action of tobacco on the oral mucosa can cause precancerous and cancerous lesions. However, there is not enough evidence to establish all the systemic effects caused by nicotine on the organism. Thus, the aim of the present study was to characterize the cellular changes of the cheek mucosa of rats submitted to long-term systemic nicotine treatment. Twenty male rats were divided into two experimental groups: a nicotine group and a control group, each consisting of 10 animals. The nicotine group was injected daily with 0.250 mg of nicotine per 100 g of body weight. All animals received a solid diet and water ad libitum. After 90 days of treatment, all animals were weighed and sacrificed. Samples of cheek mucosa were collected for light and transmission electron microscopy. The results revealed oral epithelium containing atypical cells that were characterized by atrophy, cell membrane disorganization and tissue damage. It was concluded that systemic administration of nicotine damaged the cellular integrity of the oral mucosa, impairing tissue function and predisposing the tissue to the action of different pathogenic agents and also to that of other carcinogenic substances present in tobacco.

Repair of bone defects treated with autogenous bone graft and low-power laser.

Because bone healing at the graft site is similar to a fracture repair, the purpose of the present study was to evaluate the effects of low-power laser irradiation on the repair of rat skull defects treated with autogenous bone graft. A defect measuring 3 mm in diameter was produced in the left parietal bone and filled with an autogenous bone graft obtained from the right parietal bone. The animals were divided into 3 groups of 20 rats each: nonirradiated control, irradiated with 5.1 J/cm, and irradiated with 10.2 J/cm. The laser (2.4 mW, 735 nm, 3.4 x 10 W/cm, 3-mm spot size) was applied three times per week for 4 weeks. Greater volume of newly formed bone was observed in the irradiated group with 10.2 J/cm. In both irradiated groups, a greater volume of newly formed bone occurred only in the first 2 weeks. The results demonstrated that laser irradiation at the grafted site stimulated osteogenesis during the initial stages of the healing process in a skull defect of the rat and that this effect was dose dependent.

Stereology and ultrastructure of the salivary glands of diabetic Nod mice submitted to long-term insulin treatment.

Insulin-dependent diabetes mellitus compromises the salivary glands, altering their morphology and the mechanisms of salivation, which are fundamental for oral health. Thus, the aim of the present study was to determine the effects of prolonged insulin treatment on the morphology of the salivary glands in Nod mice. Forty-five female mice were divided into five groups: nine positive diabetic Nod mice for 10 days (group 1), nine positive diabetic Nod mice for 20 days (group 2), nine diabetic Nod mice for 10 days (group 3), nine diabetic Nod mice for 20 days (group 4), and nine nondiabetic BALB/c mice (group 5). Animals of groups 3 and 4 received 4-5 U of insulin daily, whereas animals of groups 1, 2, and 5 received the same dose of physiological saline simulating the experimental conditions. Samples of the salivary glands were analyzed by light, transmission, and scanning electron microscopies. The results showed intense alterations in diabetic animals characterized by nuclear and cytoplasmic atrophy, biomembrane disorganization, an increase in fibrillar components of the extracellular matrix, and the presence of inflammatory cells. Insulin treatment exerted positive effects on the recovery of the changes resulting from the diabetic state in both parotid and submandibular glands but the pattern continued to be altered. It can be concluded that, in addition to compromising the processes of tissue maintenance and renewal, tissue destructuring leads to alterations in functional mechanisms in both diabetic animals and animals submitted to glycemic control.

Trigeminal neuralgia is caused by maxillary and mandibular nerve entrapment: greater incidence of right-sided facial symptoms is due to the foramen rotundum and foramen ovale being narrower on the right side of the cranium.

Trigeminal neuralgia (TN) is the most important disease of the trigeminal nerve. Vascular compression of the dorsal root of the trigeminal nerve by aberrant loop of blood vessels is currently accepted as the most common cause of TN. The right side of the face is affected by TN twice as often as the left side, but there are no anatomical reasons for the blood vessels loop to be more frequent on the right side of the cranial fossa. Additionally, vascular compression in asymptomatic patients and in TN patients without aberrant blood vessels has been reported, thereby arguing against the idea that vascular compression alone is responsible for TN. Anatomical and radiological studies have shown that the rotundum and ovale foramens on the right side of the human cranium are significantly narrower than on the left side. The rotundum and ovale foramens are crossed by the maxillary and mandibular nerves, respectively, and are the nerves most affected in TN. Based on demographic and epidemiological data of TN patients, and on anatomical findings in the foramens, we hypothesized that entrapment of the maxillary and mandibular nerves when they cross the ovale and rotundum foramens is a primary cause of TN and accounts for the higher incidence of TN on the right sided.

Zygomatic bone: anatomic bases for osseointegrated implant anchorage.

PURPOSE: The aim of the present study was to evaluate zygomatic bone thickness considering a possible relationship between this parameter and cephalic index (CI) for better use of CI in the implant placement technique. MATERIALS AND METHODS: CI was calculated for 60 dry Brazilian skulls. The zygomatic bones of the skulls were divided into 13 standardized sections for measurement. Bilateral measurements of zygomatic bone thickness were made on dry skulls. RESULTS: Sections 5, 6, 8, and 9 were appropriate for implant anchorage in terms of location. The mean thicknesses of these sections were 6.05 mm for section 5, 3.15 mm for section 6, 6.13 mm for section 8, and 4.75 mm for section 9. In only 1 section, section 8, did mean thickness on 1 side of of the skull differ significantly from mean thickness on the other side (P <.001). DISCUSSION: For the relationship between quadrant thickness and CI, sections 6 and 8 varied independently of CI. Section 5 associated with brachycephaly, and section 9 associated with subbrachycephaly, presented variations in the corresponding thickness. CONCLUSION: Based on the results, implants should be placed in sections 5 and 8, since they presented the greatest thickness, except in brachycephalic subjects, where thickness was greatest in section 5, and in subbrachycephalic subjects, where thickness was greatest in section 9. CI did not prove to be an appropriate parameter for evaluating zygomatic bone thickness for this sampling. (More than 50 references.)