RESUMO
BACKGROUND: We aimed to histomorphometrically evaluate the effects of Leucocyte-Platelet-Rich Fibrin (L-PRF), with and without the combination of a bone grafting material, for alveolar ridge preservation using an in vivo canine model. MATERIAL AND METHODS: Seven dogs (Female Beagles, ~18-month-old) were acquired for the study. L-PRF was prepared from each individual animal by drawing venous blood and spinning them through a centrifuge at 408 RCF-clot (IntrasSpin, Intra-Lock, Boca Raton, FL). L-PRF membranes were obtained from XPression fabrication kit (Biohorizons Implant Systems, Inc., AL, USA). A split mouth approach was adopted with the first molar mesial and distal socket defects treated in an interpolated fashion of the following study groups: 1) Empty socket (negative control); 2) OSS filled defect 3) L-PRF membrane; and 4) Mix of Bio-Oss® with L-PRF. After six weeks, samples were harvested, histologically processed, and evaluated for bone area fraction occupancy (BAFO), vertical/horizontal ridge dimensions (VRD and HRD, respectively), and area of coronal soft tissue infiltration. RESULTS: BAFO was statistically lower for the control group in comparison to all treatment groups. Defects treated with Bio-Oss® were not statistically different then defects treated solely with L-PRF. Collapsed across all groups, L-PRF exhibited higher degrees of BAFO than groups without L-PRF. Defects filled with Bio-Oss® and Bio-Oss® with L-PRF demonstrated greater maintenance of VRD relative to the control group. Collapsed across all groups, Bio-Oss® maintained the VRD and resulted in less area of coronal soft tissue infiltration compared to the empty defect. Soft tissue infiltration observed at the coronal area was not statistically different among defects filled with L-PRF, Bio-Oss®, and Bio-Oss® with L-PRF. CONCLUSIONS: Inclusion of L-PRF to particulate xenograft did not promote additional bone heading at 6 weeks in vivo. However, we noted that L-PRF alone promoted alveolar socket regeneration to levels comparable to particulate xenografts, suggesting its potential utilization for socket preservation.
Assuntos
Regeneração Óssea , Fibrina Rica em Plaquetas , Alvéolo Dental , Processo Alveolar , Animais , Cães , Feminino , Leucócitos , Dente Molar , Extração Dentária , Alvéolo Dental/cirurgiaRESUMO
BACKGROUND: Trismus-Pseudocamptodactyly Syndrome (TPS) is a rare autosomal syndrome characterised by the inability to open the mouth fully, pseudocamptodactyly, short stature and foot deformities. The maxillofacial feature entails hyperplasia of the coronoid processes which mechanically interfere with the zygomatic processes during mouth opening. CASE REPORT: A 22-year- old girl affected by a severe form of TPS was followed from the age of three years. Bone reossification was observed after two coronoidotomies of both hyperplasic coronoid processes. After the decision to perform a coronoidectomy, the four-year follow-up showed a favourable outcome. Meanwhile the patient developed an anterior open bite which was treated with a fourth orthognathic surgery. The follow-up underscores how the correction of malformation leads to the generation of EMG activity of the masticatory muscles after many years of passiveness.
Assuntos
Anormalidades Múltiplas/fisiopatologia , Artrogripose/fisiopatologia , Trismo/fisiopatologia , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/cirurgia , Adolescente , Artrogripose/diagnóstico , Artrogripose/cirurgia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Trismo/diagnóstico , Trismo/cirurgia , Adulto JovemRESUMO
OBJECTIVES: Rehabilitation of maxillary edentulism with implant-supported prostheses has come into common clinical practice. Although autologous bone has osteoinductive, osteoconductive and osteogenetic properties, its use is subject to certain disadvantages such as: Increased morbidity Limited amount of bone harvested from each donor site. AIM: The aim of this study is to analyze clinical, histological and histomorphometric results of homologous bone for implantoprosthetic rehabilitation in severe atrophic jaws. PATIENTS AND METHODS: Twenty consecutive patients, 14 female and 6 males, were treated with homologous bone bank. Treatment protocol consist of: first surgycal step, trasversal and vertical volume restore, second surgycal step: screw remove, specimen biopsy and insert implant fixtures. RESULTS: Data show that Fresh Frozen Bone Allografts (FFBA) could be a valuable substitute for autologous bone, in as much as histological and histomorphometric results are widely overlapping. CONCLUSIONS: Homologous bone is a valuable option for its large availability with a low cost, good versatility, no morbidity at the donor site, shorter surgical time and hospital stay.
Assuntos
Transplante Ósseo , Procedimentos Cirúrgicos Ortognáticos , Procedimentos de Cirurgia Plástica/métodos , Adulto , Idoso , Atrofia , Feminino , Congelamento , Humanos , Arcada Osseodentária/patologia , Masculino , Pessoa de Meia-Idade , Transplante HomólogoRESUMO
The mitochondrial DNA variation of 295 Berber-speakers from Morocco (Asni, Bouhria and Figuig) and the Egyptian oasis of Siwa was evaluated by sequencing a portion of the control region (including HVS-I and part of HVS-II) and surveying haplogroup-specific coding region markers. Our findings show that the Berber mitochondrial pool is characterized by an overall high frequency of Western Eurasian haplogroups, a somehow lower frequency of sub-Saharan L lineages, and a significant (but differential) presence of North African haplogroups U6 and M1, thus occupying an intermediate position between European and sub-Saharan populations in PCA analysis. A clear and significant genetic differentiation between the Berbers from Maghreb and Egyptian Berbers was also observed. The first are related to European populations as shown by haplogroup H1 and V frequencies, whereas the latter share more affinities with East African and Nile Valley populations as indicated by the high frequency of M1 and the presence of L0a1, L3i, L4*, and L4b2 lineages. Moreover, haplogroup U6 was not observed in Siwa. We conclude that the origins and maternal diversity of Berber populations are old and complex, and these communities bear genetic characteristics resulting from various events of gene flow with surrounding and migrating populations.
Assuntos
Genes Mitocondriais , Genética Populacional , África do Norte , Emigração e Imigração , Etnicidade , HumanosRESUMO
European populations display low genetic differentiation as the result of long-term blending of their ancient founding ancestries. However, it is unclear how the combination of ancient ancestries related to early foragers, Neolithic farmers, and Bronze Age nomadic pastoralists can explain the distribution of genetic variation across Europe. Populations in natural crossroads like the Italian peninsula are expected to recapitulate the continental diversity, but have been systematically understudied. Here, we characterize the ancestry profiles of Italian populations using a genome-wide dataset representative of modern and ancient samples from across Italy, Europe, and the rest of the world. Italian genomes capture several ancient signatures, including a non-steppe contribution derived ultimately from the Caucasus. Differences in ancestry composition, as the result of migration and admixture, have generated in Italy the largest degree of population structure detected so far in the continent, as well as shaping the amount of Neanderthal DNA in modern-day populations.
Assuntos
DNA Antigo , Bases de Dados Genéticas , Deriva Genética , Genoma Humano , População Branca/genética , Animais , Estudo de Associação Genômica Ampla , História Antiga , Genética Humana , Humanos , Itália , Homem de Neandertal/genéticaRESUMO
BACKGROUND: Overlapping phenotypes including LHON, MELAS, and Leigh syndrome have recently been associated with numerous mtDNA point mutations in the ND5 gene of complex I, now considered a mutational hot spot. OBJECTIVE: To identify the mtDNA defect in a family with a prevalent ocular phenotype, including LHON-like optic neuropathy, retinopathy, and cataract, but characterised also by strokes, early deaths, and miscarriages on the maternal line. RESULTS: Sequencing of the entire mitochondrial genome from the proband's muscle DNA identified the heteroplasmic 13042G-->A transition, which was previously described only once in a patient with a different mitochondrial disease. This mutation fulfils the major pathogenic criteria, inducing an amino acid change (A236T) at an invariant position in a highly conserved domain of the ND5 gene. Phosphorus magnetic resonance spectroscopy in the proband disclosed an in vivo brain and skeletal muscle energy metabolism deficit. CONCLUSIONS: These findings conclusively establish the pathogenic role of the 13042G-->A mutation and underscore its variable clinical expression.
Assuntos
DNA Mitocondrial/genética , Oftalmopatias/genética , Polimorfismo de Nucleotídeo Único , Pareamento Incorreto de Bases , Encéfalo/patologia , Humanos , Espectroscopia de Ressonância Magnética , Mutação , Reação em Cadeia da Polimerase , PrevalênciaRESUMO
Values of kinetic parameters for the hydrolysis of esters and p-nitroanilides of L-lysine and L-arginine catalyzed by the Lys77 form of human plasmin (EC 3.4.21.7) have been determined between pH 5.5 and 8 (I = 0.1 M) at 21 +/- 0.5 degrees C. Over the whole pH range explored, Lys77-plasmin catalysis conforms to simple Michaelis-Menten kinetics, and steady-state and pre-steady-state data may be consistently fitted to the minimum three-step mechanism: E + S in equilibrium (k+1/k-1)E X S----(k+2)E X P + P1----(k+3)E + P2 In spite of the higher specificity of lysyl derivatives for Lys77-plasmin rather than the arginyl ones, kinetic parameters also depend on the nature of the N-alpha substituent and/or of the alcoholic or p-nitroanilidic moiety of the substrate. Among the esters and anilides considered, ZLysONp shows the most favourable kinetic parameters and may be the substrate of choice of Lys77-plasmin, in that it allows the determination of the enzyme concentration as low as 2 X 10(-9) M (about 1 X 10(-3) CU/ml), at the optimum pH value (approx. 8). Between pH 5.5 and 8, the pH profiles of kcat and kcat/Km for the Lys77-plasmin-catalyzed hydrolysis of ZLysONp and ZArgONp reflect the ionization of a single group (probably His-602 involved in the active site) with pKa values ranging between 6.4 and 6.6; at variance, values of Km are pH-independent.
Assuntos
Fibrinolisina/farmacologia , Fragmentos de Peptídeos/farmacologia , Catálise , Humanos , Concentração de Íons de Hidrogênio , Hidrólise , Cinética , Lisina , Especificidade por SubstratoRESUMO
Pre-steady-state and steady-state kinetics of the papain (EC 3.4.22.2)-catalyzed hydrolysis of N-alpha-carbobenzoxyglycine p-nitrophenyl ester (ZGlyONp) have been determined between pH 3.0 and 9.5 (I = 0.1 M) at 21 +/- 0.5 degrees C. The results are consistent with the minimum three-step mechanism involving the acyl X enzyme intermediate E X P: (Formula: see text). The formation of the E X S complex may be regarded as a rapid pseudoequilibrium process; the minimum values for k+1 are 8.0 microM-1 s-1 (pH less than or equal to 3.5) and 0.40 microM-1 s-1 (pH greater than 6.0), and that for k-1 is 600 s-1 (pH independent). The pH profile of k+2/Ks (= kcat/Km; Ks = k-1/k+1) reflects the ionization of two groups with pK' values of 4.5 +/- 0.1 and 8.80 +/- 0.15 in the free enzyme. The pH dependence of k+2 and k+3 (measured only at pH values below neutrality) implicates one ionizing group in the acylation and deacylation step with pK'' values of 5.80 +/- 0.15 and 3.10 +/- 0.15, respectively. As expected from the pH dependences of k+2/Ks (= kcat/Km) and k+2, the value of Ks changes with pH from 7.5 X 10(1) microM (pH less than or equal to 3.5) to 1.5 X 10(3) microM (pH greater than 6.0). Values of k-2 and k-3 are close to zero over the whole pH range explored (3.0 to 9.5). The pH dependence of kinetic parameters indicates that at acid pH values (less than or equal to 3.5), the k+2 step is rate limiting in catalysis, whereas for pH values higher than 3.5, k+3 becomes rate limiting. The observed ionizations probably reflect the acid-base equilibria of residues involved in the catalytic diad of papain, His159-Cys25. Comparison with catalytic properties of ficins and bromelains suggests that the results reported here may be of general significance for cysteine proteinase catalyzed reactions.
Assuntos
Glicina/análogos & derivados , Homeostase , Concentração de Íons de Hidrogênio , Papaína/farmacologia , Catálise , Glicina/metabolismo , Hidrólise , CinéticaRESUMO
Four new missense mutations have been identified through restriction analysis and sequencing of the mitochondrial DNAs (mtDNA) from Leber's hereditary optic neuropathy (LHON) patients who lacked the previously identified 11778 mutation. Each altered a conserved amino acid and correlated with the LHON phenotype in population and phylogenetic analyses. The nucleotide pair (np) 13708 mutation (G to A, ND5 gene) changed an alanine to a threonine and was found in 6/25 (24%) of non-11778 LHON pedigrees and in 5.0% of controls, the np 15257 mutation (G to A, cytochrome b gene) changed an aspartate to an asparagine and was found in 4 of the 13708-positive pedigrees and 0.3% of controls, the np 15812 mutation (G to A, cytochrome b gene) changed a valine to a methionine and was detected in two of the 15257-positive pedigrees and 0.1% of controls and the np 5244 mutation (G to A, ND2 gene) changed a glycine to a serine and was found in one of the 15812-positive patients and none of 2103 controls. The 15257 mutation altered a highly conserved amino acid in an extramembrane domain of cytochrome b that is associated with the ligation of the low potential b566 heme and the 5244 mutation altered a strongly evolutionarily conserved region of the ND2 polypeptide. The 13708 and 15812 mutations changed moderately conserved amino acids. Haplotype and phylogenetic analysis of the four np 15257 mtDNAs revealed that all harbored the same rare Caucasian haplotype and that the np 13708, np 15257, np 15812 and np 5244 mutations were added sequentially along this mtDNA lineage. Since the percentage of sighted controls decreases as these mutations accumulate, it appears that they interact synergistically, each increasing the probability of blindness. The involvement of both mitochondrial complex I (np 5244, 11778, 13708) and complex III (np 15257, 15812) mutations in LHON indicates that the clinical manifestations of this disease are the product of an overall decrease in mitochondrial energy production rather than a defect in a specific mitochondrial enzyme.
Assuntos
Grupo dos Citocromos b/genética , DNA Mitocondrial/genética , Atrofias Ópticas Hereditárias/genética , RNA de Transferência de Alanina/genética , RNA de Transferência de Serina/genética , Sequência de Bases , Feminino , Haplótipos , Humanos , Masculino , Dados de Sequência Molecular , Mutação/genética , Linhagem , Filogenia , Reação em Cadeia da Polimerase , Mapeamento por Restrição , População Branca/classificação , População Branca/genéticaRESUMO
Human mitochondrial DNAs (mtDNAs) from 153 independent samples encompassing seven Asian populations were surveyed for sequence variation using the polymerase chain reaction (PCR), restriction endonuclease analysis and oligonucleotide hybridization. All Asian populations were found to share two ancient AluI/DdeI polymorphisms at nps 10394 and 10397 and to be genetically similar indicating that they share a common ancestry. The greatest mtDNA diversity and the highest frequency of mtDNAs with HpaI/HincII morph 1 were observed in the Vietnamese suggesting a Southern Mongoloid origin of Asians. Remnants of the founding populations of Papua New Guinea (PNG) were found in Malaysia, and a marked frequency cline for the COII/tRNA(Lys) intergenic deletion was observed along coastal Asia. Phylogenetic analysis indicates that both insertion and deletion mutations in the COII/tRNA(Lys) region have occurred more than once.
Assuntos
Povo Asiático/genética , DNA Mitocondrial/genética , Genética Populacional , Polimorfismo de Fragmento de Restrição , Sudeste Asiático , Povo Asiático/classificação , Frequência do Gene/genética , Variação Genética/genética , Haplótipos , Humanos , Mutação/genética , Filogenia , Reação em Cadeia da Polimerase , RNA de Transferência de Lisina/genéticaRESUMO
Mitochondrial DNA (mtDNA) sequence variation was examined in Finns, Swedes and Tuscans by PCR amplification and restriction analysis. About 99% of the mtDNAs were subsumed within 10 mtDNA haplogroups (H, I, J, K, M, T, U, V, W, and X) suggesting that the identified haplogroups could encompass virtually all European mtDNAs. Because both hypervariable segments of the mtDNA control region were previously sequenced in the Tuscan samples, the mtDNA haplogroups and control region sequences could be compared. Using a combination of haplogroup-specific restriction site changes and control region nucleotide substitutions, the distribution of the haplogroups was surveyed through the published restriction site polymorphism and control region sequence data of Caucasoids. This supported the conclusion that most haplogroups observed in Europe are Caucasoid-specific, and that at least some of them occur at varying frequencies in different Caucasoid populations. The classification of almost all European mtDNA variation in a number of well defined haplogroups could provide additional insights about the origin and relationships of Caucasoid populations and the process of human colonization of Europe, and is valuable for the definition of the role played by mtDNA backgrounds in the expression of pathological mtDNA mutations.
Assuntos
DNA Mitocondrial/análise , Genética Populacional , Sequência de Bases , DNA Mitocondrial/classificação , Europa (Continente) , Haplótipos , Humanos , Dados de Sequência Molecular , Polimorfismo GenéticoRESUMO
Mitochondrial DNAs (mtDNAs) from 167 American Indians including 87 Amerind-speakers (Amerinds) and 80 Nadene-speakers (Nadene) were surveyed for sequence variation by detailed restriction analysis. All Native American mtDNAs clustered into one of four distinct lineages, defined by the restriction site variants: HincII site loss at np 13,259, AluI site loss at np 5,176, 9-base pair (9-bp) COII-tRNA(Lys) intergenic deletion and HaeIII site gain at np 663. The HincII np 13,259 and AluI np 5,176 lineages were observed exclusively in Amerinds and were shared by all such tribal groups analyzed, thus demonstrating that North, Central and South American Amerinds originated from a common ancestral genetic stock. The 9-bp deletion and HaeIII np 663 lineages were found in both the Amerinds and Nadene but the Nadene HaeIII np 663 lineage had a unique sublineage defined by an RsaI site loss at np 16,329. The amount of sequence variation accumulated in the Amerind HincII np 13,259 and AluI np 5,176 lineages and that in the Amerind portion of the HaeIII np 663 lineage all gave divergence times in the order of 20,000 years before present. The divergence time for the Nadene portion of the HaeIII np 663 lineage was about 6,000-10,000 years. Hence, the ancestral Nadene migrated from Asia independently and considerably more recently than the progenitors of the Amerinds. The divergence times of both the Amerind and Nadene branches of the COII-tRNA(Lys) deletion lineage were intermediate between the Amerind and Nadene specific lineages, raising the possibility of a third source of mtDNA in American Indians.
Assuntos
DNA Mitocondrial/genética , Genética Populacional , Indígenas Norte-Americanos/genética , Polimorfismo de Fragmento de Restrição , Povo Asiático/genética , Evolução Biológica , Frequência do Gene/genética , Variação Genética/genética , Haplótipos , Humanos , Indígenas Norte-Americanos/classificação , Mutação/genética , América do Norte , Filogenia , RNA de Transferência de Lisina/genética , População Branca/genéticaRESUMO
Mitochondrial DNA (mtDNA) sequence variation was examined in 37 Seminoles from Florida by polymerase chain reaction amplification and high resolution restriction endonuclease analysis. The Y chromosome TaqI restriction fragment length polymorphisms detected by the probes 49a, 49f, and 12f2 were examined in the 26 males of this group. Analysis of the mtDNA revealed that all four Native American haplogroups (A, B, C and D) were present in the Seminoles encompassing about 95% of the Seminole mtDNAs. No European mtDNAs were found among the Seminoles, but two mtDNAs (about 5%) were members of the African-specific haplogroup L1, thus indicating that a limited number of African women were incorporated in the Seminole tribe. Analysis of Y chromosome haplotypes supports the hypothesis that haplotypes 18 and 63 are the most likely founding Native American Y chromosome haplotypes from Asia. However, 11% of the Seminole Y chromosomes represented haplotypes generally attributed to Europeans, though none harbored standard African haplotypes. These findings support historical evidence that the Seminole tribe has integrated individuals of European and African ancestry, but suggests that the sex ratio of nonnatives from different continents may have varied.
Assuntos
DNA Mitocondrial/ultraestrutura , Indígenas Norte-Americanos/genética , Polimorfismo Genético/genética , Cromossomo Y/ultraestrutura , DNA/análise , Feminino , Florida , Marcadores Genéticos , Variação Genética , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Polimorfismo de Fragmento de Restrição , Mapeamento por RestriçãoRESUMO
OBJECTIVE: Point mutations in mitochondrial DNA (mtDNA) are one mechanism that could explain the apparent excess maternal transmission of bipolar affective disorder observed in some families. The authors sequenced the mtDNA from probands with bipolar disorder and tested nucleotide variants for association with the disorder. METHOD: The entire 16.5 kilobase mitochondrial genome was sequenced in nine unrelated probands selected from large pedigrees with exclusively maternal transmission of bipolar affective disorder. Compared to a reference sequence, variants were detected at 107 nucleotide positions. Fifteen variants of possible pathogenic significance were selected for further study. These variants were assayed in 93 unrelated probands with bipolar I, bipolar II, or schizoaffective-manic disorder and 63 comparison subjects, all of whom were classified into the major groups comprising the European mtDNA haplotype structure (haplogroups). RESULTS: The major European haplogroups were represented at the expected frequencies among both probands and comparison subjects. There was no significant difference between probands and comparison subjects in the frequency of any variant, although odds ratios >2 or <0.5 were observed for four variants. Frequencies of these four variants were similar in probands and haplogroup-matched comparison subjects. The results of all comparisons were essentially unchanged when probands from families with an apparently paternal transmission pattern were excluded. CONCLUSIONS: The results demonstrate that bipolar affective disorder occurs across all of the major European mtDNA haplogroups but do not reveal any point mutations that explain excess maternal transmission of the disorder.
Assuntos
Transtorno Bipolar/genética , DNA Mitocondrial/genética , Adolescente , Adulto , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/epidemiologia , Estudos de Casos e Controles , Criança , Feminino , Ligação Genética/genética , Marcadores Genéticos , Variação Genética/genética , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação Puntual/genética , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Cromossomo X/genéticaRESUMO
Y-chromosome variation was analyzed in a sample of 1127 males from the Western Mediterranean area by surveying 16 biallelic and 4 multiallelic sites. Some populations from Northeastern Europe and the Middle East were also studied for comparison. All Y-chromosome haplotypes were included in a parsimonious genealogic tree consisting of 17 haplogroups, several of which displayed distinct geographic specificities. One of the haplogroups, HG9.2, has some features that are compatible with a spread into Europe from the Near East during the Neolithic period. However, the current distribution of this haplogroup would suggest that the Neolithic gene pool had a major impact in the eastern and central part of the Mediterranean basin, but very limited consequences in Iberia and Northwestern Europe. Two other haplogroups, HG25.2 and HG2.2, were found to have much more restricted geographic distributions. The first most likely originated in the Berbers within the last few thousand years, and allows the detection of gene flow to Iberia and Southern Europe. The latter haplogroup is common only in Sardinia, which confirms the genetic peculiarity and isolation of the Sardinians. Overall, this study demonstrates that the dissection of Y-chromosome variation into haplogroups with a more restricted geographic distribution can reveal important differences even between populations that live at short distances, and provides new clues to their past interactions.
Assuntos
Variação Genética , Polimorfismo Genético , Cromossomo Y/genética , África do Norte , Alelos , Europa (Continente) , Haplótipos/genética , Humanos , Masculino , Região do Mediterrâneo , Repetições de Microssatélites , Oriente Médio , Análise Multivariada , Recombinação GenéticaRESUMO
An epidemic neuropathy in Cuba has caused bilateral optic neuropathies in more than 26,000 people during the past three years. Various pathogenetic factors have been proposed, including toxins, nutritional deficiencies, and an underlying genetic predisposition involving mitochondrial DNA. As part of a case-control collaborative investigation, 135 Cuban blood samples were analyzed for the most common mitochondrial DNA mutations associated with Leber's hereditary optic neuropathy. None of the participants tested were found to have the mitochondrial DNA mutations at nucleotide positions 11778, 3460, 14484, 7444, or 9804. Of 57 definite case subjects and 69 normal control subjects, three case and three control subjects had the mutation at nucleotide position 9438, three different case and three different control subjects had the mutation at position 13708, and one case and one control subject had the mutation at position 15257 in association with the mutation at position 13708. The most common mitochondrial DNA mutations associated with Leber's hereditary optic neuropathy do not appear to be contributing factors in the epidemic neuropathy in Cuba. We also identified a large Cuban family with maternally related members who experienced visual loss consistent with the diagnosis of Leber's hereditary optic neuropathy. Maternal family members harbored the highly pathogenetic mutation at nucleotide position 11778.
Assuntos
Surtos de Doenças , Atrofias Ópticas Hereditárias/genética , Doenças do Nervo Óptico/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Cuba/epidemiologia , DNA Mitocondrial , Eletroforese em Gel de Ágar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Atrofias Ópticas Hereditárias/epidemiologia , Atrofias Ópticas Hereditárias/etiologia , Doenças do Nervo Óptico/etiologia , Doenças do Nervo Óptico/genética , Linhagem , Reação em Cadeia da PolimeraseRESUMO
Exposure of the distal internal carotid artery at the level of the second cervical vertebra required manoeuvers such as division of digastric muscle or mandibular subluxation. These increase the exposure but may not provide adequate access and are associated with significant cranial nerves or temporal mandibular joint complications. Vertical Ramus Osteotomy (VRO) provided access of the internal carotid artery (ICA) up to the base of the skull, with low incidence of cranial nerve injury temporo-mandibular joint (TMJ) pain and no preincision preparation. We report two cases in which vertical division of the mandibular ramus provided access of the ICA up to the base of the skull. Preoperative Duplex Scan examination and in the second case the arteriography revealed ICA preocclusive stenosis within 1.5 cm of the skull base. VRO was performed trouhgh a standard neck incision and miniature titanium plates were used to reapproximate the mandible after vascular procedure. There were no death, cranial nerve injury, mandibular nonunion, malocclusion or TMJ pain. We found that VRO is useful when carotid artery pathology extends beyond the usual field of exposure, avoiding nerve injury or TMJ lesion and requires no additional pre-incision preparation.
Assuntos
Artéria Carótida Interna/cirurgia , Mandíbula/cirurgia , Osteotomia , Procedimentos Cirúrgicos Vasculares , Idoso , Angiografia , Estenose das Carótidas/cirurgia , Feminino , Humanos , Masculino , Mandíbula/anatomia & histologiaRESUMO
OBJECTIVE: To investigate the mechanisms underlying myoclonus in Leber hereditary optic neuropathy (LHON). METHODS: Five patients and one unaffected carrier from two Italian families bearing the homoplasmic 11778/ND4 and 3460/ND1 mutations underwent a uniform investigation including neurophysiologic studies, muscle biopsy, serum lactic acid after exercise, and muscle ((31)P) and cerebral ((1)H) magnetic resonance spectroscopy (MRS). Biochemical investigations on fibroblasts and complete mitochondrial DNA (mtDNA) sequences of both families were also performed. RESULTS: All six individuals had myoclonus. In spite of a normal EEG background and the absence of giant SEPs and C reflex, EEG-EMG back-averaging showed a preceding jerk-locked EEG potential, consistent with a cortical generator of the myoclonus. Specific comorbidities in the 11778/ND4 family included muscular cramps and psychiatric disorders, whereas features common to both families were migraine and cardiologic abnormalities. Signs of mitochondrial proliferation were seen in muscle biopsies and lactic acid elevation was observed in four of six patients. (31)P-MRS was abnormal in five of six patients and (1)H-MRS showed ventricular accumulation of lactic acid in three of six patients. Fibroblast ATP depletion was evident at 48 hours incubation with galactose in LHON/myoclonus patients. Sequence analysis revealed haplogroup T2 (11778/ND4 family) and U4a (3460/ND1 family) mtDNAs. A functional role for the non-synonymous 4136A>G/ND1, 9139G>A/ATPase6, and 15773G>A/cyt b variants was supported by amino acid conservation analysis. CONCLUSIONS: Myoclonus and other comorbidities characterized our Leber hereditary optic neuropathy (LHON) families. Functional investigations disclosed a bioenergetic impairment in all individuals. Our sequence analysis suggests that the LHON plus phenotype in our cases may relate to the synergic role of mtDNA variants.
Assuntos
DNA Mitocondrial/genética , Metabolismo Energético/genética , Predisposição Genética para Doença/genética , Mutação/genética , Mioclonia/genética , Atrofia Óptica Hereditária de Leber/genética , Trifosfato de Adenosina/deficiência , Adulto , Análise Mutacional de DNA , Eletroencefalografia , Eletromiografia , Feminino , Frequência do Gene , Testes Genéticos , Genótipo , Humanos , Padrões de Herança/genética , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Mioclonia/fisiopatologia , Atrofia Óptica Hereditária de Leber/complicações , Atrofia Óptica Hereditária de Leber/fisiopatologia , Linhagem , RecidivaRESUMO
The variation at 28 Y-chromosome biallelic markers was analysed in 256 males (90 Croats, 81 Serbs and 85 Bosniacs) from Bosnia-Herzegovina. An important shared feature between the three ethnic groups is the high frequency of the "Palaeolithic" European-specific haplogroup (Hg) I, a likely signature of a Balkan population re-expansion after the Last Glacial Maximum. This haplogroup is almost completely represented by the sub-haplogroup I-P37 whose frequency is, however, higher in the Croats (approximately 71%) than in Bosniacs (approximately 44%) and Serbs (approximately 31%). Other rather frequent haplogroups are E (approximately 15%) and J (approximately 7%), which are considered to have arrived from the Middle East in Neolithic and post-Neolithic times, and R-M17 (approximately 14%), which probably marked several arrivals, at different times, from eastern Eurasia. Hg E, almost exclusively represented by its subclade E-M78, is more common in the Serbs (approximately 20%) than in Bosniacs (approximately 13%) and Croats (approximately 9%), and Hg J, observed in only one Croat, encompasses approximately 9% of the Serbs and approximately 12% of the Bosniacs, where it shows its highest diversification. By contrast, Hg R-M17 displays similar frequencies in all three groups. On the whole, the three main groups of Bosnia-Herzegovina, in spite of some quantitative differences, share a large fraction of the same ancient gene pool distinctive for the Balkan area.