Delivery Mode and Neurological Complications in Very Low Birth Weight Infants.

OBJECTIVE: The risk of intraventricular hemorrhage (IVH) and periventricular leukomalacia is associated with low birth weight and gestational age. Caesarean section (CS) may reduce the risk of IVH, although it has been a matter of debate. The aim of this study was to evaluate the influence of the mode of delivery (MOD) on the development of IVH and cystic periventricular leukomalacia (cPVL). STUDY DESIGN: We analyzed an initial cohort of 11,023 very low birth weight (VLBW) infants born between January 2010 and December 2019. Infants with major malformations and gestational age <23 weeks and ≥32 weeks were excluded. A final cohort of 8,251 newborns was analyzed. Data was collected from Portuguese National very low birth weight registry. Cases were classified as vaginal delivery (VD) or CS. Outcome was assessed in univariate and logistic regression analyses. RESULTS: The median gestational age was 29 weeks (IQR 3.3) and the median weight was 1,100 g (IQR 555). The prevalence of IVH was significantly higher in the VD group versus the CS group, across all grading levels:1,144 newborns had grade I IVH (16% VD vs. 14% CS, p <0.01), 706 had grade II IVH (12% VD vs. 7.6% CS, p <0.01), and 777 had grade III IVH (14% VD vs. 7.9% CS, p <0.01). Post-hemorrhagic ventricular dilatation occurred in 457 newborns (8.3% VD vs. 4.6% CS, p <0.01) and 456 newborns had periventricular hemorrhagic infarction (8.4% VD vs. 4.5% CS, p <0.01). There was no association between MOD and cPVL. After applying a logistic regression analysis, including known risk factors for IVH and cPVL, VD was independently associated with an increased risk of IVH (odds ratio [OR] 1.600[1.423-1.799], p <0.001) and its complications (OR 1.440[1.195-1.735], p <0.001). MOD was not associated with an increased risk of cPVL. CONCLUSION: Our study suggests that CS is associated with a reduced risk of IVH and its complications in preterm VLBW infants < 32 weeks of gestational age. A CS should be considered in this group of infants to prevent the development of IVH and its complications. KEY POINTS: · IVH and cPVL are risk factors for neurological disabilities.. · CS may decrease the risk of IVH in preterms <32 weeks GA.. · There is no association between the MOD and cPVL..

Case Report of a Neonate Born to a Mother with Severe SARS-CoV-2 Infection under ECMO.

Neonatal SARS-CoV-2 infections are rare and although there is some evidence of vertical transmission, most newborns show no clinical signs or present with only mild clinical symptoms. Fetal survival is reported around 70% in mothers submitted to extracorporeal membrane oxygenation. We present a case of a male newborn born at 29 weeks from a mother under extracorporeal membrane oxygenation due to SARS-CoV-2 infection. There was no evidence of vertical transmission, polymerase chain reaction testing of nasopharyngeal/throat swab and polymerase chain reaction testing of blood sample for SARS-CoV-2 were both negative. On day 2, he developed signs of osteomyelitis of the distal femur extremity, which resolved after six weeks of antibiotic therapy, with no other significant events during admission. This case report depicts the favorable outcome of a live infant born to a mother with severe SARS-CoV-2infection under extracorporeal membrane oxygenation.

A infeção neonatal por SARS-CoV-2 é rara e apesar de existir alguma evidência da possibilidade de transmissão vertical, a maioria dos recém-nascidos não manifesta quaisquer sinais clínicos ou apresenta apenas sintomas ligeiros. A sobrevivência fetal é de aproximadamente 70% para grávidas que tenham necessitado de oxigenação por membrana extracorporal. Apresentamos um caso de um recém-nascido do sexo masculino, nascido às 29 semanas de idade gestacional de uma mãe sob oxigenação por membrana extracorporal, devido a infeção por SARS-CoV-2. Não se verificou evidência de transmissão vertical, e a reação em cadeia da polimerase de amostras nasofaríngeas e sanguíneas foi negativa. No segundo dia de vida desenvolveu sinais compatíveis com osteomielite da extremidade distal do fémur, resolvidos após seis semanas de antibioticoterapia, sem outras intercorrências relevantes durante a admissão. Este caso revela uma evolução clínica favorável de um recém-nascido, filho de mãe com infeção grave por SARS-CoV-2 sob oxigenação por membrana extracorporal.

GLP-1 improves adipose tissue glyoxalase activity and capillarization improving insulin sensitivity in type 2 diabetes.

Methylglyoxal was shown to impair adipose tissue capillarization and insulin sensitivity in obese models. We hypothesized that glyoxalase-1 (GLO-1) activity could be diminished in the adipose tissue of type 2 diabetic obese patients. Moreover, we assessed whether such activity could be increased by GLP-1-based therapies in order to improve adipose tissue capillarization and insulin sensitivity. GLO-1 activity was assessed in visceral adipose tissue of a cohort of obese patients. The role of GLP-1 in modulating GLO-1 was assessed in type 2 diabetic GK rats submitted to sleeve gastrectomy or Liraglutide treatment, in the adipose tissue angiogenesis assay and in the HUVEC cell line. Glyoxalase-1 activity was decreased in visceral adipose tissue of pre-diabetic and diabetic obese patients, together with other markers of adipose tissue dysfunction and correlated with increased HbA1c levels. Decreased adipose tissue GLO-1 levels in GK rats were increased by sleeve gastrectomy and Liraglutide, being associated with overexpression of angiogenic and vasoactive factors, as well as insulin receptor phosphorylation (Tyr1161). Moreover, GLP-1 increased adipose tissue capillarization and HUVEC proliferation in a glyoxalase-dependent manner. Lower adipose tissue GLO-1 activity was observed in dysmetabolic patients, being a target for GLP-1 in improving adipose tissue capillarization and insulin sensitivity.

Performance of Intergrowth 21st Growth Charts in the Diagnosis of Small and Large for Gestational Age in Term and Preterm Newborns.

INTRODUCTION: Birth weight is a major contributor to neonatal morbidity and mortality and is associated with chronic diseases in adulthood. This study aimed to evaluate the use of Intergrowth 21st instead of the Fenton & Kim 2013 growth charts in the diagnosis of small and large for gestational age in a group of Portuguese newborns. MATERIAL AND METHODS: We conducted an analytical and retrospective study to evaluate birth weight of term and preterm newborns using both growth charts. Groups studied: 'Term-weeks' and 'Term-days' (term newborns with gestational age in weeks and days, respectively), 'Preterm-weeks' and 'Preterm-days' (preterm newborns with gestational age in weeks and days, respectively). RESULTS: A total of 14 056 newborns were included, 6% preterm. Using the Intergrowth 21st growth charts, the groups 'Term-weeks' (n = 12 081), 'Term-days' (n = 1118), 'Preterm-weeks' (n = 617) and 'Preterm-days' (n = 240), classified as small for gestational age according to the Fenton & Kim 2013 growth charts were adequate for gestational age in 52.8%, 57.8%, 37.7% and 9.3% respectively; and 9.2%, 9.2%, 5.9% and 0.6% of adequate for gestational age newborns were large for gestational age, respectively. In the 'Pretermdays' group, 7.9% of adequate for gestational age newborns were small for gestational age and 22.2% of large for gestational age newborns were adequate for gestational age, all with gestational age below 231 days. DISCUSSION: The use of the Intergrowth 21st growth charts in this sample resulted in a lower number of newborns being classified as small for gestational age, except in very preterm newborns. CONCLUSION: Considering the results obtained, we suggest that Portuguese maternity hospitals use the Intergrowth 21st instead of the Fenton & Kim 2013 growth charts. However, more studies are needed to confirm these results.

[Morbidity in Prematurity Associated with Fetal Growth Restriction: Experience of a Tertiary Care Center]. / Morbilidade na Prematuridade Associada a Restrição do Crescimento Fetal e nos Prematuros Leves para a Idade Gestacional: Experiência de um Centro de Referência.

INTRODUCTION: Prematurity and low birth weight have been associated with increased neonatal morbidity and mortality. This study aimed to evaluate possible risk factors for prematurity associated with fetal growth restriction and being small for gestational age and to determine the incidence of morbidity in these two groups of infants. MATERIAL AND METHODS: Retrospective case-control study of newborns with gestational age of less than 32 weeks, with obstetric diagnosis of fetal growth restriction and with the clinical diagnosis of small for gestational age, admitted to the Neonatal Intensive Care Unit of a tertiary hospital for a period of six years. RESULTS: A total of 356 newborns were studied, with an incidence of 11% of fetal growth restriction and 18% of small for gestational age. Pre-eclampsia was the risk factor for gestation with higher statistical significance (47% vs 16%, p < 0.001) in small for gestational age newborns. There was also a higher incidence of mild bronchopulmonary dysplasia (66% vs 38%, p = 0.005), late sepsis (59% vs 37%, p = 0.003), retinopathy of prematurity (58% vs 26%, p = 0.003) and necrotizing enterocolitis (20% vs 9%, p = 0.005). Mortality was similar in all three groups. DISCUSSION: There were fewer newborn males diagnosed with fetal growth restriction during pregnancy compared to women. Significant differences were observed in the group of these infants regarding the occurrence of chorioamnionitis and pre-eclampsia in comparison to the control group. Newborns with fetal growth restriction and small for age had higher scores on clinical risk indices compared to the control group. In general, small for gestational age newborns had a higher incidence of morbidity than infants with fetal growth restriction and the control group. CONCLUSION: Advances in neonatal intensive care decreased mortality in preterm infants. However, there are still significant differences in the incidence of morbidity in newborns with growth compromise. The collaboration between obstetricians and neonatologists provides the basis for a correct clinical evaluation, early signaling and global intervention on these newborns, with a significant impact on short and long-term prognosis.

Introdução: A prematuridade e o baixo peso ao nascer têm sido associados a maior morbilidade e mortalidade neonatais. Este estudo teve como objetivo avaliar possíveis fatores de risco para a prematuridade associada a restrição do crescimento fetal e a recém-nascidos leves para a idade gestacional e determinar a incidência da morbilidade nestes dois grupos de recém-nascidos.Material e Métodos: Estudo caso-controlo retrospetivo dos recém-nascidos com idade gestacional inferior a 32 semanas, com o diagnóstico obstétrico de restrição do crescimento fetal e com o diagnóstico clínico de leves para a idade gestacional, internados na Unidade de Cuidados Intensivos Neonatais de um hospital terciário, durante um período de seis anos.Resultados: Foram estudados 356 recém-nascidos, observando-se uma incidência de 11% de restrição do crescimento fetal e 18% de leves para a idade gestacional. A pré-eclâmpsia foi o fator de risco da gestação com maior significado estatístico (47% vs 16%, p < 0,001) nos recém-nascidos leves para a idade gestacional. Observou-se também, nestes recém-nascidos, maior incidência de displasia broncopulmonar ligeira (66% vs 38%, p = 0,005), de sépsis tardia (59% vs 37%, p = 0,003), de retinopatia da prematuridade (58% vs 26%, p = 0,003) e de enterocolite necrotizante (20% vs 9%, p = 0,005). A mortalidade foi idêntica nos três grupos.Discussão: Encontraram-se menos recém-nascidos do sexo masculino diagnosticados com restrição do crescimento fetal durante a gravidez comparativamente ao sexo feminino. Observaram-se diferenças significativas no grupo destes recém-nascidos, quanto à ocorrência de corioamnionite e de pré-eclâmpsia, face ao grupo controlo. Tanto os recém-nascidos com restrição do crescimento fetal como os leves para a idade gestacional apresentaram uma pontuação mais elevada nos índices de risco clínico comparativamente ao grupo controlo. De forma global, os recém-nascidos leves para a idade gestacional tiveram maior incidência de morbilidade que os recém-nascidos com restrição do crescimento fetal e que o grupo controlo.Conclusão: Os avanços nos cuidados intensivos neonatais diminuíram a mortalidade nos recém-nascidos prematuros. Contudo, observam-se ainda diferenças significativas na incidência da morbilidade nos recém-nascidos com compromisso do crescimento. A colaboração entre obstetras e neonatalogistas constitui a base para uma correta avaliação clínica, sinalização precoce e intervenção global sobre estes recém-nascidos, com impacto significativo no prognóstico a curto e longo prazo.

Dental caries and bacterial load in saliva and dental biofilm of type 1 diabetics on continuous subcutaneous insulin infusion.

OBJECTIVES: Since most of the studies evaluates diabetics on multiple daily injections therapy and continuous subcutaneous insulin infusion may help gain better metabolic control and prevent complications, the objective of this study was to evaluate the prevalence of dental caries, the unstimulated salivary flow rate and the total bacteria load, Streptococcus spp. levels and Lactobacillus spp. levels in saliva and supragingival dental biofilm of type 1 diabetics on insulin pump. MATERIAL AND METHODS: Sixty patients with type 1 diabetes on insulin pump and 60 nondiabetic individuals were included. The dental caries evaluation was performed using ICDAS and the oral hygiene was assessed according to Greene and Vermillion Simplified Oral Hygiene Index. Unstimulated saliva and supragingival dental biofilm were collected. Total bacteria, Streptococcus spp. and Lactobacillus spp. was quantified by qPCR. RESULTS: Patients with type 1 diabetes had a higher prevalence of dental caries and filled and missing teeth when compared with the control group. These patients were associated with more risk factors for the development of dental caries, namely a lower unstimulated salivary flow rate and a higher bacterial load in saliva and dental biofilm. CONCLUSION: Some risk factors related to dental caries were associated with type 1 diabetics. An early diagnosis combined with the evaluation of the risk profile of the diabetic patient is imperative, allowing the dental caries to be analyzed through a perspective of prevention and the patient to be integrated into an individualized oral health program.

Dental caries and bacterial load in saliva and dental biofilm of type 1 diabetics on continuous subcutaneous insulin infusion

Abstract Objectives Since most of the studies evaluates diabetics on multiple daily injections therapy and continuous subcutaneous insulin infusion may help gain better metabolic control and prevent complications, the objective of this study was to evaluate the prevalence of dental caries, the unstimulated salivary flow rate and the total bacteria load, Streptococcus spp. levels and Lactobacillus spp. levels in saliva and supragingival dental biofilm of type 1 diabetics on insulin pump. Material and Methods Sixty patients with type 1 diabetes on insulin pump and 60 nondiabetic individuals were included. The dental caries evaluation was performed using ICDAS and the oral hygiene was assessed according to Greene and Vermillion Simplified Oral Hygiene Index. Unstimulated saliva and supragingival dental biofilm were collected. Total bacteria, Streptococcus spp. and Lactobacillus spp. was quantified by qPCR. Results Patients with type 1 diabetes had a higher prevalence of dental caries and filled and missing teeth when compared with the control group. These patients were associated with more risk factors for the development of dental caries, namely a lower unstimulated salivary flow rate and a higher bacterial load in saliva and dental biofilm. Conclusion Some risk factors related to dental caries were associated with type 1 diabetics. An early diagnosis combined with the evaluation of the risk profile of the diabetic patient is imperative, allowing the dental caries to be analyzed through a perspective of prevention and the patient to be integrated into an individualized oral health program.

[Being a Mother After 35 Years: Will it be Different?] / Ser Mãe Depois dos 35 Anos: Será Diferente?

INTRODUCTION: Advanced maternal age is defined as maternity after 35 years old and is associated with more complications during pregnancy and neonatal period as well as decreased fertility. This study aims to examine the relationship between advanced maternal age and their maternal and fetal consequences, as well as maternal perception of the risk of pregnancy after 35 years old. MATERIAL AND METHODS: Observational, retrospective and comparative study, between two groups: advanced maternal age group (aged ≥ 35 years) and non-advanced maternal age group (age < 35 years), conducted between March and June 2015. Chi-square test and Fisher's exact test were used and considered significant if p < 0.05. RESULTS: Of the 736 women admitted to the hospital (32.2% with advanced maternal age), 306 were included in the study (153 in each group). In the non-advanced maternal age group there was a greater number of primiparous women (p < 0.01). In the advanced maternal age group, more previous miscarriages were observed (p < 0.001), as well as a higher use of assisted reproductive techniques (p < 0.01), preformed of amniocentesis (p < 0.001) and dystocia, including caesarean sections (p < 0.001). No association was found regarding the presence of maternal complications in pregnancy, birth defects, need for neonatal resuscitation or prematurity. As for the perception of risk in pregnancy, the non-advanced maternal age group considered it to be superior (p < 0.05). DISCUSSION: Most women of advanced maternal age have term deliveries without complications. Neonatal outcomes seem not to have been influenced by the advanced maternal age. CONCLUSION: The consequences of an advanced maternal age pregnancy in this sample did not have the same clinical expression as described in the literature. In the future, advanced maternal age will possibly be considered after age 40.

Introdução: A idade materna avançada corresponde à maternidade depois dos 35 anos. Está associada a maior número de complicações na gravidez e período neonatal e ainda à diminuição da fertilidade. Propôs-se analisar a relação entre idade materna avançada e suas consequências materno-fetais, assim como a perceção materna dos riscos de uma gravidez depois dos 35 anos. Material e Métodos: Estudo observacional, retrospetivo, descritivo e comparativo entre dois grupos: Grupo idade materna avançada (idade ≥ 35 anos) e Grupo não-idade materna avançada (idade < 35 anos), efetuado entre março e junho de 2015. Utilizado o teste do qui-quadrado e teste exato de Fisher e considerado significativo se p < 0,05. Resultados: Das 736 puérperas internadas (32,2% com idade materna avançada), 306 foram incluídas no estudo (153 em cada grupo). No grupo não-idade materna avançada verificou-se um maior número de primíparas (p < 0,01). No grupo idade materna avançada observou-se um maior número de abortos espontâneos prévios (p < 0,001) e foi superior o recurso a técnicas de reprodução medicamente assistida (p < 0,01), a realização de amniocentese (p < 0,001) e o número de partos distócicos, nomeadamente cesarianas (p < 0,001). Não se encontraram diferenças em relação à presença de patologia materna na gravidez, malformações congénitas, necessidade de reanimação neonatal ou prematuridade. Quanto à perceção do risco numa gravidez em idade materna avançada, o grupo não-idade materna avançada considerou-o superior (p < 0,05). Discussão: A maior parte das mulheres em idade materna avançada tiveram partos de termo e sem complicações. Os resultados neonatais parecem não ter sido influenciados pela idade materna avançada. Conclusão: As consequências de uma gravidez em idade materna avançada na nossa amostra não tiveram a mesma expressão clínica que as descritas na literatura. No futuro, a idade materna avançada será possivelmente considerada após os 40 anos.

Histologic evaluation of the effect of mineral trioxide aggregate-Fillapex as a root canal sealer in rat teeth submitted to late replantation.

OBJECTIVE: This study aims to analyze the effect of new root canal based silicate cement, in rat teeth after late replantation, comparing with calcium hydroxide (CH) in preventing tooth root resorption. MATERIALS AND METHODS: The study group included 16 Wistar rats in which the upper right central incisors were extracted and were left on a worktable for 60 min, simulating a case of tooth avulsion, after had been anesthetized. One group, (Group I), the canals were filled with CH past, before replantation. The second groups of teeth, (Group II), the canals were filled with mineral trioxide aggregate-Fillapex (MTAF). After removal, the blood clot of the socket, with saline solution irrigation, the teeth were replanted into their original socket, and splinted with silk 3/0. The rats were sacrificed 8 weeks after replantation and the specimens were prepared for histologic and histomorphometric analyses. The areas of inflammatory and replacement resorptions were selected and quantified. These data for each group of teeth were evaluated and analyzed using the Mann-Whitney test (P = 0.05). RESULT AND CONCLUSION: All the replanted teeth in both groups survived. Although root canal filled with MTAF provide better results than with CH past concerning inflammatory and replacement resorption, there was no statistical difference (P = 0.527).

Sealing efficacy of system B versus Thermafil and Guttacore obturation techniques evidenced by scintigraphic analysis.

BACKGROUND: This study compared root canal sealing ability, filled by Continuous Wave compaction and two carrier-based obturation systems, using the nuclear medicine approach. MATERIAL AND METHODS: Fifty-five single-rooted extracted teeth were selected. The crowns were sectioned and each tooth was instrumented using rotary Protaper® Universal system. The roots were divided into 3 experimental groups and two control groups. Forty-five root canals were filled, using Continuous Wave, GuttaCore or Thermafil system and TopSeal sealer. Ten teeth were used as control. On the 7th days the apices were submersed in a solution of sodium pertechnetate 99mTc for 3 hours and the radioactivity was counted. RESULTS: Although apical leakage in the Continuous Wave group was lower compared with GuttaCore and Thermafil groups, there was no statistical difference (p>0.05). CONCLUSIONS: System B, GuttaCore and Thermafil techniques showed a similar sealing effect. Key words:Continuous wave compaction, Gutta percha core-carrier, leakage, nuclear medicine.

In vivo biodistribution of antihyperglycemic biopolymer-based nanoparticles for the treatment of type 1 and type 2 diabetes.

This study aimed to assess the biodistribution of antihyperglycemic insulin-loaded alginate/dextran sulfate-based nanoparticles dual coated with chitosan and technetium-99m-albumin (99mTc-BSA) after oral administration. The oral administration of 50IU/kg insulin-loaded nanoparticles to type 1 diabetic rats showed prolonged antihyperglycemic effects up to 12h and relative pharmacological availability of 5.04% comparing to the subcutaneous administration. The oral antihyperglycemic effect was further compared between type 1 and type 2 diabetic models by the intraperitoneal glucose tolerance test, revealing that the effect lasted longer in the type 1 diabetic model. 99mTc-BSA revealed to be a good nanoparticles' tracer since there was no systemic absorption and 99mTc-BSA-nanoparticles were capable of increasing their residence time in the intestinal epithelium of balb-c mice when compared with 99mTc-BSA biodistribution. Thus, this biopolymeric-based delivery nanoparticulate system is a promising tool for the therapy of type 1 and type 2 diabetic individuals and prevention of T1D.

Invasive fungal infection in neonatal intensive care units: a multicenter survey.

This study assesses the epidemiology of invasive fungal infection (IFI) in Portuguese Neonatal Intensive Care Units (NICUs) and compares the effectiveness and safety of antifungal therapies. A survey concerning the period 2005-2010 was carried out in NICUs of Greater Lisbon. Among 10 473 admitted neonates, 44 cases were identified, 29 among extreme low birth weight neonates (65.9%). Cumulative incidence rate was 0.42% (95%CI 0.309-0.559). A central vascular catheter was present before IFI in all cases. Candida albicans and Candida parapsilosis were the most frequent isolates. The initial antifungic was fluconazole in 22 cases and liposomal amphotericin B (L-AmB) in 18. Therapy was switched in 10 patients on fluconazole and 3 on L-AmB. Case fatality rate was 11.4% (95%CI 4.39-23.91). No serious adverse drugs reactions (SADRs) or clinical side effects were observed. The knowledge of the local epidemiology helps to identify adequate prophylactic and treatment strategies.

An unusual cause of neonatal cyanosis .

We report a case of a female neonate whose pulse oximetry screening for congenital heart disease at 40 h of life was positive. The pregnancy was uneventful with no relevant family history. The neonate presented with bluish discolouration of the skin lasting until day 15. Cardiovascular examination and chest radiography were normal. Septic screening was negative. Oxygen therapy was started with poor response; investigations revealed a methaemoglobinaemia of 7.4%. The methaemoglobin level reached a peak of 15% on day 10, falling thereafter. The infant was discharged by day 20 with a normal physical examination and a methaemoglobinaemia of 11.4%. By 2 months of age this had fallen to 2.4%. Further investigation revealed a haemoglobin M variant: a heterozygous mutation of the γ globin gene known as Hb F-M Viseu. The mutation occurs in the γ chain, therefore the methaemoglobinaemia is transitory, resolving with the transition from fetal to adult haemoglobin.

2-Bromo-5-hydroxyphenylporphyrins for photodynamic therapy: photosensitization efficiency, subcellular localization and in vivo studies.

BACKGROUND: Photodynamic therapy (PDT) is a therapeutic modality capable of inducing cell death by oxidative stress through activation of a sensitizer by light. Aryl-porphyrin with hydroxyl groups are good photosensitizers and presence of bromine atoms can enhance the photodynamic activity through heavy atom effect. These facts and our previous work made pertinent to compare the photodynamic capacity of tetraaryl brominated porphyrin (TBr4) with the corresponding diaryl (BBr2) derivative. METHODS: Cell cultures were incubated with the sensitizers, ranging from 50nM to 10µM and irradiated until 10J. Cell proliferation was analysed by MTT assay. Flow cytometry studies evaluated cell death pathways, mitochondrial membrane potential and ROS. For in vivo studies Balb/c nu/nu mice were injected with 4×10(6)cells. After PDT, monitoring was carried out for 12 days to establish Kaplan-Meier survival curves. Tumours were excised and histological analysis was performed. RESULTS: Both sensitizers seem to accumulate in the mitochondria. The molecules have no intrinsic cytotoxicity or in non-tumour cells at therapeutic concentrations. Both sensitizers induced a significant decrease of cell proliferation and growth of xenografts of melanoma and colorectal adenocarcinoma. Diaryl BBr2 is more efficient than tetraaryl TBr4, concerning intracellular ROS production, mitochondrial disruption and induction of cell death. The main cell death pathway is necrosis. CONCLUSIONS: TBr2 and BBr4 are promising sensitizers with good photodynamic properties and have the ability to induce cell death in human melanoma and colorectal adenocarcinoma in vitro and in vivo. We consider that BBr2 is a molecule that should be the subject of extensive studies towards clinical use.

Quantitative scintigraphic analysis of pulp revascularization in autotransplanted teeth in dogs.

OBJECTIVE: The purpose of this study was to evaluate the pulpal changes associated with autogenous single-rooted immature tooth transplantation in dogs, using either one, or two-stage surgical techniques. METHODS: Teeth from 3 beagle dogs, 5 months old, were extracted and transplanted to mechanically prepared recipient sockets. Group (A), where the teeth were transplanted using a one-stage method to recipient beds prepared immediately before transplantation. Group (B), where the teeth were transplanted using a two-stage method in which the recipient beds were prepared and left to heal for 7 days before transplantation. Clinical examinations were done every week during 9 weeks. After 9 weeks, the animals were injected with 99(m)Technetium hydroxylmethylene diphosphonate (99(m)Tc-HMDP) and 3h after injection, a whole body scintigraphic acquisition was performed. After scintigraphic acquisition the animals were euthanized and the teeth extracted and its radioactivity counted in a well counter calibrated to 99(m)Tc. With the data obtained, the percentage of activity injected was calculated for each tooth. The data for each group of teeth were evaluated and analyzed using the Mann-Whitney test (p=0.05). RESULTS: All the transplanted teeth in both groups survived. No statistically significant difference was found in the absorption of the 99(m)Tc-HMDP, between the treatment groups (p=0.464) and between them and the control group (Group A vs. control p=0.713 and Group B vs. control p=0.157). CONCLUSIONS: This study demonstrated that there was no difference between the two surgical techniques in terms of the pulp revascularization in transplanted teeth.

In vitro photodynamic activity of 5,15-bis(3-hydroxyphenyl)porphyrin and its halogenated derivatives against cancer cells.

5,15-Diarylporphyrins (1-5) with hydroxyl groups and halogens as substituents were prepared by condensation between unsubstituted dipyrromethane and halogenated m-hydroxybenzaldehydes. Photophysical properties show that the nonhalogenated porphyrin 1 has higher fluorescence yield but lower singlet oxygen formation quantum yield than the halogenated derivatives due to the heavy atom effect. The in vitro activity of these derivatives was tested against WiDr colorectal adenocarcinoma and A375 melanoma cancer cells. All porphyrins present a much higher phototoxicity than Photofrin with IC(50) values lower than the 50 nM level for WiDr cells and 25 nM level for A375 cancer cells. The most photoactive compound is the nonhalogenated porphyrin 1 which also presents the highest uptake. Halogenated derivatives present much lower uptakes than 1. However, their photoactivity is similar to compound 1 showing that their intrinsic photoactivity (ISP) is very high. Iodinated compound 4 presents the highest ISP. The greater ability of these porphyrins to destroy cancer cells could be related to their photophysical and photochemical properties.

Dynamics of CD86 expression on allergic inflammation--new insights.

CD86 is a well-known costimulatory molecule in its interaction with CD28 and/or CTLA present on T cells, and is essential for full activation of naïve T-cell and subsequent differentiation. Usually the B7 molecules are expressed mainly on APCs and B cells and in specific conditions on other activated cells. These costimulatory molecules are involved in the development of allergic inflammation and airways hyperreactivity (AHR) in allergen-challenged mice. Activated T cells, CD4(+)CD25(+), express CD86 in the first 60 minutes after the specific inhalatory exposure. These T cells can be relevant in IgE mediated allergic reaction possibly by an autocrine costimulation via CD28/CTLA activation pathway. The blockage of the expression of CD86 could be a potential therapeutical target to reduce the magnitude or the progression of the allergic reaction. The review article also discussed relevant patents.

Brain blood flow SPET imaging in heroin abusers.

To assess whether chronic heroin abuse may generate vascular central nervous deficits, we studied the profile of vascular alterations in 17 heroin addicts (14 males mean age 31 years, range 23-39 years and 3 females mean age 33 years, range 30-35 years) before and, in one of them, 10 weeks after an ultra-rapid heroin detoxification. Using the functional technique of single-photon emission tomography (SPET) with 740 MBq of (99m)Tc-hexametazine (HMPAO) and computational brain-mapping techniques by means of a Talairach analysis, we determined the pattern of vascular brain alterations associated with chronic heroin abuse. Compared with controls, subjects who had used heroin chronically showed a decrease of global brain perfusion that was more significant in the frontal cortex-mainly in orbito-frontal regions, as well as in the occipital and temporal lobes. All patients showed marked asymmetric perfusion of the basal ganglia and the majority of them showed also an asymmetric perfusion of cerebellum. In addition, there were small activated areas dispersed in the occipital lobe (3 of 17) and apex region (4 of 17). In conclusion, decreased perfusion in heroin addicts was found in regions involved in the control of attention, motor speed, memory and visual-spatial processing. The prefrontal cortex is involved in decision making and inhibitory control, processes disturbed in heroin addicts who have stopped heroin consumption. A reduction in regional perfusion may reflect ongoing subtle neurocognitive deficits, which are consistent with the maintenance of asymmetry of the basal nuclei.