Squamous cell carcinoma and basal cell carcinoma of the lips: 25 years of experience in a northeast Brazilian population.

BACKGROUND: The lips are the transition zone between the facial skin and the oral mucosa and are the site of alterations related to a broad spectrum of etiologies. Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are the most prevalent neoplasms affecting lips. This study evaluated the demographic and clinicopathological features of the SCC and BCC in the lip. MATERIAL AND METHODS: A retrospective cross-sectional descriptive study (1994-2019) was carried out. Demographic and clinicopathologic data were collected from a hospital's dermatological service and an oncologic hospital. The data were submitted to descriptive analysis and Pearson's chi-square and Fisher's exact tests (p ≤ 0.05). RESULTS: 417 medical records were analyzed, of which 323 corresponded to SCC (77.5%) and 94 to BCC (22.5%). SCC showed more frequency in males (58.8%) and BCC in females (54.3%). The lower lip was significantly affected in male patients (p < 0.0001) and by both neoplasms (70.6% and 56.4%, respectively; p = 0.014). SCC and BCC were mainly treated with surgery (88.3% and 93.2%, respectively). Surgical margin was frequently negative in SCC and BCC (87%; 72.3%, respectively), and no recurrence was observed in 79.9% of SCC and 69.1% of BCC cases. CONCLUSIONS: SCC was more frequent in male patients, while BCC showed more frequency in female patients. Both neoplasms mainly affect the lower lip. Understanding the epidemiological profile of these lesions in the lip, as well as their etiology and clinical features, is fundamental for appropriate clinical conduct and the creation and/or amplification of preventive measures.

The stromal immunoexpression of CLIC4 may be related to the difference in the biological behavior between oral squamous cell carcinoma and oral verrucous carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) has high morbidity and mortality rates while oral verrucous carcinoma (OVC), an uncommon variant of OSCC, exhibits a distinct biological behavior. CLIC4 protein plays a role in the cell cycle and apoptosis regulation and participates in the myofibroblasts transdifferentiation process, which are the main cells of the tumor stroma. This study analyzed the immunoexpression of CLIC4 and α-SMA in 20 OSCC cases and 15 OVC cases. MATERIAL AND METHODS: A semiquantitative analysis of CLIC4 and α-SMA immunoexpression was performed in the parenchyma and stroma. Nuclear and cytoplasmic reactivity was analyzed separately for the CLIC4 immunostaining. The data were submitted to Pearson's chi-square and Spearman's correlation tests (p ≤ 0.05). RESULTS: In the CLIC4 analysis, there was a significant difference in the immunoexpression of this protein between OSCC and OVC stroma (p < 0.001). It was observed a higher expression of α-SMA in the OSCC stroma. There was a positive and significant correlation between CLIC4 and α-SMA immunoexpression in the OVC stroma (r = 0,612; p = 0,015). CONCLUSIONS: The decrease or absence of nuclear CLIC4 immunoexpression in the neoplastic epithelial cells and the increase of its expression in the stroma may influence the difference in biological behavior between OSCC and OVC.

Peripheral ossifying fibroma: A 20-year retrospective study with focus on clinical and morphological features.

BACKGROUND: Peripheral Ossifying Fibroma (POF) is a reactive hyperplastic lesion that exclusively occurs in the gingiva and is characterized by the deposition of dystrophic calcification, cementum-like tissue, and immature and mature bone within the connective tissue. The objective of the present study was to perform a retrospective analysis of clinicopathologic features of POF. MATERIAL AND METHODS: Clinical and histopathological data were obtained from biopsy records and histopathological reports from a Brazilian reference service in Oral Pathology (1999 - 2020). Morphological analysis was performed to evaluate features related to the mesenchymal component, inflammatory infiltrate, ulceration, and mineralized tissue. RESULTS: A total of 270 POFs were diagnosed during the study period. A higher frequency was observed in females (71.9%) between the third (22.9%) and fourth (23.3%) decades of life. The anterior upper gingiva (29.1%) was the most affected region. Mature (86.7%) and immature (52.6%) bone tissue were the most frequent. There was a significant association between immature bone deposition and lesions with size ≤ 1.7 cm (p = 0.041); immature bone and cement-like tissue deposition with an evolution time ≤ 16 months (p < 0.001); deposition of immature bone and mesenchymal hypercellularization (p < 0.001); deposition of dystrophic calcification and the presence of ulceration (p < 0.001). CONCLUSIONS: The clinical characteristics corroborate the findings in the literature. The heterogeneous distribution and quantity of mineralized tissues found in the analyzed cases support the theory that the different mineralized tissues constitute a spectrum of clinical maturation of POF.

Angina bullosa haemorrhagica: A 14-year multi-institutional retrospective study from Brazil and literature review.

BACKGROUND: Angina bullosa haemorrhagica (ABH) is characterized by the recurrent appearance of blood blisters on the oral mucosa, mainly in adults' soft palate. In general, the blisters rupture spontaneously, lacking the necessity for biopsy. We report the clinical features of 23 ABH cases, emphasizing the clinical behavior and the management of these conditions. MATERIAL AND METHODS: A retrospective descriptive cross-sectional study was performed. A total of 12,727 clinical records of oral and maxillofacial lesions from four dental services in Brazil were analyzed. Clinical data were collected from the clinical records and evaluated. RESULTS: The series comprised 12 males (52.2%) and 11 females (47.8%), with a mean age of 56.8 ± 14.6 years (ranging: 24-82 years) and a 1.1:1 male-to-female ratio. Most of the lesions affected the soft palate (n = 15, 65.2%). Clinically, the lesions presented mainly as an asymptomatic (n = 17, 73.9%) blood-filled blister that ruptured after a few minutes or hours, leaving an erosion. The masticatory trauma was the most frequent triggering event. No patient had coagulation disorders. A biopsy was performed in only four cases (17.4%). Treatment was symptomatic with a favorable outcome. CONCLUSIONS: ABH is still poorly documented in the literature, and its etiology remains uncertain. ABH mainly affects the soft palate of elderly adults and has a favorable evolution in a few days. The therapeutic approach is often focused only on the relief of symptoms. However, it can share some clinical features with more serious diseases. Therefore, clinicians must recognize these lesions to avoid misdiagnosis.

Clinicopathologic features of nasopalatine duct cysts: A retrospective study in two Brazilian oral and maxillofacial pathology referral centers.

BACKGROUND: Nasopalatine duct cyst (NDC) is the most common non-odontogenic cyst in the oral cavity. Clinically it is not difficult to suspect these lesions based on clinical and radiographic appearance. However, the histopathological diagnosis may be difficult due to the broad morphological diversity of these lesions. The objective was to analyze the clinicopathological features of NDCs diagnosed in two oral and maxillofacial pathology services in the Brazilian northeast. MATERIAL AND METHODS: A retrospective clinicopathologic study was performed. A total of 18,121 clinical records of oral lesions from two oral and maxillofacial pathology services in Brazil were analyzed (2000-2020). All NDCs cases were revised and demographic, clinical, radiographic, and histopathological data were collected. RESULTS: Among 18,121 diagnoses in the oral pathology services, 45 (0.2%) were NDCs. The series comprises 24 males (53.3%) and 21 females (46.7%), with a mean age of 43.2 years-old. Most lesions were asymptomatic (n = 27, 60%) with an mean size of 2.1 cm. Microscopically, the non-keratinized stratified squamous epithelium was the most common (66.7%). However, in 88.9% of cases, the epithelial lining was varied and composed of two or more types of epithelium. There was no significant association between the type of epithelium and the size of the cysts (p = 0.389). Nerve, blood vessels, hemorrhage, and chronic inflammatory infiltrate were commonly observed. In contrast, there was a low frequency of mucous glands, sebaceous glands, cholesterol clefts, and multinucleated giant cells. CONCLUSIONS: The clinical, radiographic, and microscopic findings observed in this study are similar to those reported in the literature. Due to the morphological diversity of NDC, it is needed to correlate its histopathological features with the clinical and radiographic findings to establish a correct diagnosis.

Dermoid and epidermoid cysts of the oral cavity: a 48-year retrospective study with focus on clinical and morphological features and review of main topics.

BACKGROUND: Dermoid and epidermoid cysts are slow-growing, benign developmental cysts that arise from ectodermal tissue and can occur anywhere in the body. Less than 7% of these cysts involve the head and neck region, with only 1.6% of cases presenting in the oral cavity. To evaluate the clinical and histopathological features of dermoid (DCs) and epidermoid (ECs) cysts stored in the archives of a referred Oral Pathology Service over a 48-year-period, and to review current concepts about these cysts. MATERIAL AND METHODS: All DCs and ECs were reviewed, and clinical data were obtained from the patient records. Fourteen cases of DCs and thirteen cases of ECs were re-evaluated microscopically by 2 oral pathologists. RESULTS: Among 15.387 cases, 14 (0.09%) had a histopathological diagnosis of DCs and 13 (0.08%) of ECs. For DCs, ten (71.4%) patients were women, with the mean age of 37.2 years. All DCs were lined by a stratified squamous epithelium (100%), with gut and respiratory epithelium observed in 1 (7.1%) and 2 (14.3%) cases, respectively. Chronic inflammatory cells, melanin, multinucleated giant cell reaction, and Pacini bodies were also observed. For ECs, eight (61.5%) cases were in women, and the mean age was 38.2 years. All ECs were lined by a stratified squamous epithelium (100%). Chronic inflammatory cells, melanin pigmentation, and adipose tissue were observed in the fibrous capsule. CONCLUSION: Our results suggest that stratified squamous epithelium is the predominant epithelial lining of these cystic lesions. Also, we may find some unusual findings in DCs, such as Pacini bodies.

A retrospective 11-year study on lip lesions attended at an oral diagnostic service.

BACKGROUND: The objective of this study was to describe the upper and lower lip lesion occurrence in an oral diagnostic service. MATERIAL AND METHODS: Retrospective descriptive sectional study was performed. Clinical records were obtained from the archives of an Oral Diagnostic Service referral center between 2006 and 2016. Data such as gender, age, anatomical location, and diagnosis were collected and categorized. The collected data were submitted to a descriptive analysis and Pearson's chi-square test (p ≤ 0.05). RESULTS: A total of 587 patient records of lip lesions were analyzed. Most lesions were diagnosed in female (52.1%) and adults (56.9%) patients in the lower lip (76.2%). Among all lip lesions, the reactive/inflammatory lesions (n = 238; 40.5%) and oral potentially malignant disorders (n = 164; 28%) were the most frequent group lesions. Mucocele (n = 147; 25%), actinic cheilitis (n = 136; 23.1%) and vascular lesions (n = 51; 8.7%) were the most frequent lesion in the sample. Actinic cheilitis was significant in relation to gender (p < 0.001), all three most frequent lesions were significant in concerning to age group and anatomical site. CONCLUSIONS: Mucocele was the most common lower lip lesion in all age groups, followed by actinic cheilitis and vascular lesions, which mainly affected adults and the elderly.

Epidemiologic study of odontogenic and non-odontogenic cysts in children and adolescents of a Brazilian population.

BACKGROUND: the objective of this study was to describe the frequency of cystic lesions in a Brazilian population of patients histopathologically diagnosed in the first and second decade of life. MATERIAL AND METHODS: Retrospective descriptive cross-sectional study was performed. Biopsy records were obtained from the archives of a Brazilian referral center between 1980 and 2016. RESULTS: A total of 2.114 biopsy records of pediatric patients were analyzed with oral and maxillofacial lesions. Data such as gender, age, anatomical location, and histopathological diagnosis were collected and categorized. Among all oral and maxillofacial lesions (n=2.114), were diagnosed 294 cases of odontogenic cysts (13.9%) and 16 cases of non-odontogenic cysts (0.8%). The most frequent lesions in each group were, respectively: radicular cyst (n=145) and epidermoid cyst (n=4). These lesions were most common in female (n=158), with a mean age of 14 years. For intraosseous lesions, the mandible (n=148) was the most affected anatomic site; moreover, the floor of the mouth (n=6) was most affected by cysts in soft tissues. CONCLUSIONS: Odontogenic cysts were relatively common in population studied, but non-odontogenic cysts were rare in these patients.

Polymorphism in the A2M gene associated with high-quality milk in Murrah buffaloes (Bubalus bubalis).

The study of genes associated with host defense mechanisms, such as the A2M gene, plays a critical role in preventing diseases that reduce milk yield and its constituents. The aim of this study was to identify polymorphisms in the A2M gene in Murrah buffaloes (Bubalus bubalis), and investigate their associations with milk yield, fat and protein production, fat and protein percentages, and somatic cell count. Hair follicle samples of 136 animals were collected for DNA extraction, and polymorphisms were identified by polymerase chain reactions and sequencing. Statistical analyses were performed to ascertain the allelic and genotypic frequencies, the Hardy-Weinberg equilibrium, and association analysis was conducted between the polymorphisms and the traits studied. Comparative analysis between buffalo and bovine sequences revealed seven nucleotide substitutions. Alignments among the buffalo sequences identified three single nucleotide polymorphisms (SNPs), including one in exon 29, g.241A>G, which was used in subsequent statistical analyses. A Hardy-Weinberg test indicated that this SNP was in equilibrium in this population, and was significantly associated (P < 0.05) with fat production and fat and protein percentages. Therefore, this SNP can be used as a molecular marker for these traits.

Role of leptin in body temperature regulation and lipid metabolism following splenectomy.

OBJECTIVE: The physiological changes in serum triglycerides and body temperature that are induced by splenectomy are poorly understood. Therefore, the aim of this study was to investigate parameters related to lipid and glucose metabolism, as well as thermoregulation, in splenectomized mice. DESIGN AND METHODS: Splenectomized and sham-operated WT mice (C57Bl/6) and ob/ob mice were randomly divided and treated with a standard or high fat diet, and several metabolic parameters and the body temperature were investigated. RESULTS: Splenectomy induced a significant increase in triglyceride levels regardless of the diet. It was found that the splenectomized WT mice showed greater serum leptin and insulin levels compared with the sham-operated mice. Additionally, the body temperatures of the splenectomized WT mice were greater than the body temperatures of the control animals regardless of diet; this result too was observed without any significant change in the temperature of the splenectomized ob/ob animals. CONCLUSION: The results suggest that splenectomy interferes with serum triglyceride metabolism and body temperature regardless of the fat content in the diet and that leptin is involved in the regulation of body temperature related to splenectomy.

Assessment of aerobic capacity during swimming exercise in ob/ob mice.

Obesity is a highly prevalent condition associated with several diseases. Physical exercise has been considered as a non-pharmacological tool in the treatment of obesity. However, several aspects underlying exercise evaluation and prescription in obesity and associated pathologies are still under investigation. Although many research involving exercise have been performed in animal models, there is a lack of protocols for aerobic capacity assessment in obese animals, such as the ob/ob mice. This study aimed the following: (i) to verify the possibility of determining the lactate threshold (LT) on swimming exercise in ob/ob mice and in non-obese heterozygote mice (ob/OB), through visual inspection (vLT) and polynomial adjustment (pLT); and (ii) to verify if the LT determined through these protocols corresponds to the maximal lactate steady state (MLSS). Eight ob/ob and ten ob/OB mice performed an incremental exercise test to determine vLT and pLT as well as constant-load exercise bouts to determine MLSS. There were no within-group differences between vLT, pLT and MLSS [ob/ob: ~5.3% body weight (BW); ob/OB: ~3·6%BW] with a high agreement among protocols. In conclusion, the identification of the LT and MLSS intensities was possible for both groups. These data suggest that the proposed protocols may be used in new research on the effects of different exercise intensities on some aspects of obesity.

Leucurogin, a new recombinant disintegrin cloned from Bothrops leucurus (white-tailed-jararaca) with potent activity upon platelet aggregation and tumor growth.

Disintegrins and disintegrins-like proteins are able to inhibit platelet aggregation and integrin-mediated cell adhesion. The aim of this study was to produce one disintegrin-like cloned from Bothrops leucurus venom gland and to characterize it regarding biological activity. The recombinant protein was purified by one step procedure involving anion-exchange chromatography (DEAE-cellulose) and presented a molecular mass of 10.4 kDa. The purified protein was able to inhibit platelet aggregation induced by collagen (IC50 = 0.65 µM) and to inhibit growth of Ehrlich tumor implanted in mice by more than 50% after 7 days administration of 10 µg/day. No effects were observed upon adenosine 5'-diphosphate (ADP)-and arachidonic acid (AA)-induced platelet aggregation. The recombinant protein was recognized by an antibody specific for jararhagin one metalloproteinase isolated from Bothrops jararaca venom, and therefore it was named leucurogin. Anti-angiogenesis effect of leucurogin was evaluated by the sponge implant model. After 7 days administration leucurogin inhibited, in a dose dependent way, the vascularization process in the sponge. Leucurogin represents a new biotechnological tool to understand biological processes where disintegrins-like are involved and may help to characterize integrins that can be involved in development and progression of malignant cells.

Plasma Kallikrein and Angiotensin I-converting enzyme N- and C-terminal domain activities are modulated by the insertion/deletion polymorphism.

Angiotensin I-converting enzyme (ACE) is recognized as one of the main effector molecules involved in blood pressure regulation. In the last few years some polymorphisms of ACE such as the insertion/deletion (I/D) polymorphism have been described, but their physiologic relevance is poorly understood. In addition, few studies investigated if the specific activity of ACE domain is related to the I/D polymorphism and if it can affect other systems. The aim of this study was to establish a biochemical and functional characterization of the I/D polymorphism and correlate this with the corresponding ACE activity. For this purpose, 119 male brazilian army recruits were genotyped and their ACE plasma activities evaluated from the C- and N-terminal catalytic domains using fluorescence resonance energy transfer (FRET) peptides, specific for the C-domain (Abz-LFK(Dnp)OH), N-domain (Abz-SDK(Dnp)P-OH) and both C- and N-domains (Abz-FRK(Dnp)P-OH). Plasma kallikrein activity was measured using Z-Phe-Arg-AMC as substrate and inhibited by selective plasma kallikrein inhibitor (PKSI). Some physiological parameters previously described related to the I/D polymorphism such as handgrip strength, blood pressure, heart rate and BMI were also evaluated. The genotype distribution was II n=27, ID n=64 and DD n=28. Total plasma ACE activity of both domains in II individuals was significantly lower in comparison to ID and DD. This pattern was also observed for C- and N-domain activities. Difference between ID and DD subjects was observed only with the N-domain specific substrate. Blood pressure, heart rate, handgrip strength and BMI were similar among the genotypes. This polymorphism also affected the plasma kallikrein activity and DD group presents high activity level. Thus, our data demonstrate that the I/D ACE polymorphism affects differently both ACE domains without effects on handgrip strength. Moreover, this polymorphism influences the kallikrein-kinin system of normotensive individuals.

Efficient method for obtaining Lep(ob)/Lep(ob)-derived animal models using adipose tissue transplantations.

BACKGROUND: Leptin-deficient mice (Lep(ob)/Lep(ob), also known as ob/ob) are of great importance for studies of obesity, diabetes and other correlated pathologies. Thus, generation of animals carrying the Lep(ob) gene mutation as well as additional genomic modifications has been used to associate genes with metabolic diseases. However, the infertility of Lep(ob)/Lep(ob) mice impairs this kind of breeding experiment. OBJECTIVE: To propose a new method for production of Lep(ob)/Lep(ob) animals and Lep(ob)/Lep(ob)-derived animal models by restoring the fertility of Lep(ob)/Lep(ob) mice in a stable way through white adipose tissue transplantations. METHODS: For this purpose, 1 g of peri-gonadal adipose tissue from lean donors was used in subcutaneous transplantations of Lep(ob)/Lep(ob) animals and a crossing strategy was established to generate Lep(ob)/Lep(ob)-derived mice. RESULTS: The presented method reduced by four times the number of animals used to generate double transgenic models (from about 20 to 5 animals per double mutant produced) and minimized the number of genotyping steps (from 3 to 1 genotyping step, reducing the number of Lep gene genotyping assays from 83 to 6). CONCLUSION: The application of the adipose transplantation technique drastically improves both the production of Lep(ob)/Lep(ob) animals and the generation of Lep(ob)/Lep(ob)-derived animal models.

Efeito da superovulação sobre o desempenho de bovinos doadores de embrião importados de clima temperado para clima tropical nos dois primeiros anos de adaptação

The results of a multiple ovulation and embryo transfer (MOET) program, obtained in its first two years, were evaluated. The donor heifers were imported already pregnant from Hungary to the North-East area of Brazil. Comparisons of the results obtained in 1996 and 1997 with superovulation programs with AUSA-Superov (FSH) and Folligon (eCG) were made. The number of CL found on both ovaries was 5.3 (FSH) and 4.2 (eCG) in 1996, and 8.2 (FSH) and 9.6 (eCG) in 1997, while the number of degenerated eggs and embryos was 2.8 (FSH) and 3.8 (eCG) in 1996, and 6.5 (FSH) and 7.4 (eCG) in 1997. The number of good quality embryos was 1.9 (FSH) and 2.3 (eCG) in 1996, and 5.5 (FSH) and 4.0 (eCG) in 1997. The embryo collection efficiency was 40% (FSH) and 35% (eCG) in 1996, and 85% (FSH) and 83% (eCG) in 1997. Significant differences were found for all results obtained in 1996 and 1997 (P 0.05). Two new commercial products were used in 1997, Pluset and Folltropin-V, both with FSHp. With Pluset therapy the number of unfertilized eggs and degenerated embryos harvested was 11.7 per retrieval, while the number of good quality embryos was 5.1 per retrieval. With Folltropin therapy the number was 4.5 and 1.9, respectively, showing that better results were obtained with Pluset (P 0.05).

Avaliou-se o desempenho de fêmeas bovinas doadoras de embrião nos primeiros dois anos de trabalho em um centro do programa multiple ovulation and embryo transfer (MOET). Utilizaram-se novilhas prenhes de recente importação de clima moderado para o Nordeste Brasileiro. Compararam-se os resultados de superovulação em 1996, primeiro ano de adaptação dos animais, e 1997 com AUSA-Superov (FSH) e Folligon (eCG). O número de CL contados no ovário foi 3,3 (FSH) e 4,2 (eCG) em 1996 e 8,2 (FSH) e 9,6 (eCG) em 1997, o de óvulos e embriões degenerados coletados de 2,8 (FSH) e 3,8 (eCG) em 1996 e 6,5 (FSH) e 7,4 (eCG) em 1997, o de embriões de boa qualidade de 1,9 (FSH) e 2,3 (eCG) em 1996 e 5,5 (FSH) e 4,0 (eCG) em 1997. A eficiência da coleta foi de 40% (FSH) e 35% (eCG) em 1996 e 85% (FSH) e 83% (eCG) em 1997. Todos os valores citados para 1996 e 1997 foram significativamente diferentes (P 0,05). Em 1997 foram utilizados dois produtos novos, Pluset e Folltropin-V, ambos à base de pFSH. Com Pluset o número de óvulos e embriões degenerados lavados foi de 11,7 unidades/doadora e o número de embriões de boa qualidade foi de 5,1 unidades/lavagem. Com Folltropin-V, o número foi de 4,5 unidades/lavagem e o de embriões viáveis de 1,9 unidades/doadora. Melhores resultados foram obtidos com Pluset (P 0,05).