Antiapoptotic and antioxidant effects of carvedilol and vitamin E protect against diabetic nephropathy and cardiomyopathy in diabetic Wistar albino rats.

Carvedilol is a novel ß-adrenoreceptor blocker, with antioxidant properties inhibiting lipid peroxidation and preventing the depletion of endogenous antioxidants. Moreover, carvedilol was reported to enhance the expression of Bcl-2 gene, which has antioxidant and antiapoptotic effects. There are few researches testing the protective effect of carvedilol on the development of diabetic cardiomyopathy and nephropathy. In this study, we induced diabetes mellitus in male Wistar albino rats. We investigated carvedilol, as well as vitamin E, administrated in healthy and diabetic rats for 6 weeks to compare their effects on biochemical parameters and the expression of Bcl-2 protein in both myocardial and renal tissues by immunohistochemistry. The study showed that the diabetic rats not only had renal dysfunction and more myocardial damage, but also showed lower expression of Bcl-2 protein. Carvedilol and vitamin E treatments were associated with better renal function and less myocardial damage, lower blood glucose, and lipid peroxidation, higher antioxidant capacity, better serum lipids, and higher expression of Bcl-2 protein in diabetic rats. These results indicate that carvedilol and vitamin E treatments partly protect against myocardial and renal damage probably via their antioxidant and antiapoptotic properties in diabetic rats.

Pro- and anti-inflammatory cytokine gene single-nucleotide polymorphisms in inflammatory bowel disease.

Anti-inflammatory cytokines have an important role in disease, tumour and transplant processes. Alterations in the regulation of several cytokines have been implicated in a variety of inflammatory disorders, including IBD (inflammatory bowel disease) [Crohn's disease (CD) and ulcerative colitis (UC)]. Cytokine polymorphisms are also known to affect the level of gene expression. Thus, the aim of this study was to determine the relationship between cytokine polymorphisms and the IBD pathologies in a Spanish population. Polymorphisms analysis was performed using PCR-SSOP using a microbeads luminex assay. The following polymorphisms were determined: TNFα [-238G/A (rs361525) and -308G/A (rs1800629)], IFNγ [+874A/T (rs62559044)], TGFß [+869C/T (rs1982073) and +915G/C (rs1800471)], IL10 [-1082A/A (rs1800896), -592A/C (rs1800872), -819C/T (rs1800871)], IL6 [-174C/G (rs1800795)], IL12p40 [3'UTR -1188A/C (rs3212227)], IL1α [-889C/T (rs1800587)], IL1ß [-511C/T (rs1143634) and +3962C/T (rs1143633)], IL1R [Pst-1 1970C/T] and IL1RA [Mspa-1 11100C/T]. No statistical differences in TNFα, IFNγ, TGFß, IL10, IL6, IL1α, IL1ß, IL1R and IL1Ra genotypes and allele distributions between the IBD groups and healthy controls were found. However, we observed significant differences in the 3'UTR -1188A/C polymorphism of IL12p40. So -1188A allele was increased in patients with UC and the -1188C allele (high IL12p40 production) was increased in patients with CD with respect to controls. These data are in concordance with the fact that CD has been shown to be associated with a Th1 T-cell-mediated inflammation model and high IL12/IFNγ production at histological affected sites. These data suggest that cytokine polymorphisms in TNFα, IFNγ, TGFß, IL10, IL6 and IL1α, IL1ß, IL1R and IL1Ra cytokine gene do not seem to be relevant in IBD susceptibility and IL12p40 3'UTR -1188A/C polymorphism seems to be associated with a differential IBD development.

Genetic polymorphisms of tumour necrosis factor alpha (TNF-α) promoter gene and response to TNF-α inhibitors in Spanish patients with inflammatory bowel disease.

Tumour necrosis factor alpha (TNF-α) has an important role in inflammatory response. Alterations in the regulation of TNF-α have been implicated in a variety of inflammatory disorders, including Inflammatory bowel disease (IBD). Indeed, a common treatment for IBD is the use of TNF-α inhibitors. Polymorphisms in the TNF-α promoter region are known to affect the level of gene expression. Our aim was to investigate the influence of these single nucleotide polymorphisms (SNPs) in TNF-α promoter gene play in the risk of IBD in a Spanish population and their individual response to anti-TNF-α treatment. DNA samples from patients with IBD and controls were screened for TNF-α -238G/A (rs361525) and -308G/A (rs1800629) SNPs by PCR-SSOP using a microbeads luminex assay and compared with response to TNF-α inhibitors. There were not statistical differences in -238G/A and -308G/A allele and genotype frequencies between patients. However, we found an increased frequency of -308A allele and -308GA genotype in these nonresponders patients to TNF-α inhibitors with respect to responders patients (Pc < 0.05). This -308GA genotype has been classified as high producer of this cytokine. This fact could actually be interesting to explain the different response of patients with IBD with respect to TNF-α inhibitors. TNF-α promoter gene polymorphism does not seem to play a role in IBD susceptibility, but particular TNF-α genotypes may be involved in the different responses to TNF-α inhibitor treatment in Spanish patients with IBD.

Prosthetic Maintenance Assessment for Two Implant- Retained Overdentures Reinforced with PEKK Versus Co-Cr Framework: A Randomized Controlled Clinical Trial.

INTRODUCTION: The primary challenge associated with implant overdentures lies in the occurrence of denture fractures around the attachments. Hence, it is recommended to enhance flexural strength through reinforcement frameworks. This study aimed to assess and compare the prosthetic maintenance of mandibular implant overdentures reinforced with Co-Cr and PEKK frameworks. METHODS: Twenty-four participants with completely edentulous ridges were selected, and two implants were placed at the mandibular canine areas. After osseointegration period, ball attachments were installed. Participants were randomly assigned into two groups: Group I received a mandibular implant overdenture reinforced with a Co-Cr framework, while Group II received a mandibular implant overdenture reinforced with a PEKK framework. Prosthetic maintenance evaluations were conducted in both groups twelve months post-denture insertion. Categorical data were analyzed, and results were presented as frequency and percentage values. RESULTS: Group II exhibited a significantly higher percentage of cases with screw looseness, denture relining, and tooth separation compared to Group I. Although Group II cases showed a non-significant increase in the percentage of insert wear and retention loss. CONCLUSION: Within the limitations of this study, the findings suggest that Co-Cr, in contrast to PEKK frameworks, offers a more reliable reinforcement of the implant-retained overdentures.

Lift-off protocols for thin films for use in EXAFS experiments.

Lift-off protocols for thin films for improved extended X-ray absorption fine structure (EXAFS) measurements are presented. Using wet chemical etching of the substrate or the interlayer between the thin film and the substrate, stand-alone high-quality micrometer-thin films are obtained. Protocols for the single-crystalline semiconductors GeSi, InGaAs, InGaP, InP and GaAs, the amorphous semiconductors GaAs, GeSi and InP and the dielectric materials SiO2 and Si3N4 are presented. The removal of the substrate and the ability to stack the thin films yield benefits for EXAFS experiments in transmission as well as in fluorescence mode. Several cases are presented where this improved sample preparation procedure results in higher-quality EXAFS data compared with conventional sample preparation methods. This lift-off procedure can also be advantageous for other experimental techniques (e.g. small-angle X-ray scattering) that benefit from removing undesired contributions from the substrate.

Socioeconomic risk factors for low birth weight newborns: A population-based study.

Low birth weight (LBW) is an important indicator of maternal health and poverty. This study explored the socioeconomic factors associated with LBW. METHODS: Data was collected from a 4-year maternal-newborn registry. RESULTS: There were 5,316 LBW and 54,029 normal birth weight (NBW). The prevalence of LBW was 9%. The Native women in the LBW group compared to non-native women were 10.4% (1784/5316) vs. 8.4% (3532/5316) with a P-value of 0.001. There were more illiterate mothers in the LBW compared to the NBW, respectively: 8.1% (1597/19497) vs. 7.5% (1763/23230) with a P-value of 0.001. Working mothers tend to have more LBW infants compared to mothers with NBW, 8.4% (1588/17217) vs. 7.9% (2532/31891) and P-value 0.001. Young mothers (<20 years old) with early childbearing had more LBW compared to older mothers, respectively 12.7% (180/1414) vs. 8.9% (5149/52919) P-value <0.001. Women with no antenatal care reported a high rate of LBW compared to women with regular antenatal care: 14.2% (516/3696) vs. 8.6% (4741/55691) P-value <0.001. LBW babies were born more from assisted conception pregnancies (38% compared to 8.4% of normal pregnancies) P-value <0.001. Smoking mothers scored higher with LBW at 13.6% vs. 8.3% and a P-value of 0.001. There were no differences between the two groups regarding religion, consanguinity, marital status, or family income. CONCLUSION: Risk factors for low birth weight can be improved by providing antenatal care, smoking cessation, optimizing high-risk pregnancy care, and governing assisted reproduction regulations.

Prolonged empiric antibiotics and time to full enteral feed in preterm infants less than 29 weeks of gestational age.

BACKGROUND: Early empiric antibiotic exposure appears to negatively influence feeding tolerance in preterm infants. However, the effect of prolonged antibiotic treatment is unknown. The objective of this study was to investigate whether prolonged antibiotics impact the time to full enteral feed in infants less than 29 weeks of gestational age with negative blood cultures. METHODS: Retrospective data for infants less than 29 weeks gestation age were retrieved from the PEARL-Peristat perinatal registry in Qatar. Exclusion criteria were major congenital anomalies, conditions requiring surgery in the first 10 days of life, positive blood cultures in the first 48 hours of life, and death within the first week of life. Antibiotic courses were categorized as prolonged if continued more than 48 hours. The primary outcome was the duration of total parenteral nutrition. RESULTS: Of 199 study infants, 185 (92.9%) underwent antibiotic treatment for > 48 hours despite negative blood cultures. The median duration of parenteral nutrition was not significantly different between the prolonged and short antibiotic groups (25 and 22 days, respectively; p = 0.139). Infants with prolonged antibiotic courses experienced non-significantly higher levels of necrotizing enterocolitis (7.1% and 18.4%, respectively), bronchopulmonary dysplasia (28.6% and 45.4%, respectively), and retinopathy of prematurity (14.3% and 38.4%, respectively). There were no differences in the late-onset sepsis rate (78.6% and 82.1%, respectively) and the in-hospital death rate (7.1% and 7.6%, respectively). CONCLUSIONS: Prolonged antibiotic treatment in infants less than 29 weeks gestation with negative blood cultures has no significant impact on the time to full enteral feed.

Development of dorzolamide hydrochloride in situ gel nanoemulsion for ocular delivery.

BACKGROUND: Several in situ gel-forming systems have been developed to prolong the precorneal residence time of a drug and to improve ocular bioavailability. Poloxamer 407 with its thermoreversible gelation and surface active properties was utilized to formulate a novel dorzolamide hydrochloride in situ gel nanoemulsion (NE) delivery system for ocular use. OBJECTIVE: Improvement of both ocular bioavailability and duration of action for dorzolamide hydrochloride was the aim of this study. METHODS: Physicochemical properties, in vitro drug release studies and biological evaluation of the prepared NEs were investigated. RESULTS: The optimum formulation of in situ gel NE consisted of Triacetin (7.80%), Poloxamer 407 (13.65%), Poloxamer 188 (3.41%), Miranol C2M (4.55%), and water (70.59%). Biological evaluation of the designed dorzolamide formulation on normotensive albino rabbits indicated that this formulation had better biological performance, faster onset of action, and prolonged effect relative to either drug solution or the market product. The formula showed a superior pharmacodynamic activity compared to the in situ gel dorzolamide eye drops. This indicated the effectiveness of the in situ gel properties of poloxamer 407, besides formulating the drug in an NE form for improving the therapeutic efficacy of the drug. CONCLUSION: These results demonstrate the superiority of in situ gel NE to conventional ocular eye drops and in situ gels to enhance ocular drug bioavailability.

Selection criteria for resuscitation and survivability rates for neonates at the limit of viability.

AIM: To evaluate outcomes of a cohort of infants born at 23 weeks' gestational age after introducing a new selection score for resuscitation in the delivery room (DR). METHODS: This was a retrospective charts review study using data from the maternal and newborn registry funded by the Qatar National Research Fund. Parents were consulted prenatally and their wishes were honored. The plan of resuscitation was based on the new selection score. The seven components of the score were four antenatal and three immediate postnatal in the DR. Each component received a score of zero, one, or two according to its presence, uncertainty or absence, respectively. Only a score of≥7 would receive active resuscitation unless specified otherwise during prenatal consultation. RESULTS: The study reviewed 60 infants that were delivered over a two year period. The DR death rate was 23 of 60 (38%). Thirty-seven infants (61%) were admitted to the NICU. The score was applied only on 37 infants where all score criteria were reported in their files. Twenty infants had score <7; of them 13 (65%) died in the DR and 7 were admitted to NICU of whom two (29%) survived to discharge. Seventeen babies with scores≥7 admitted to NICU of whom nine (51%) survived to discharge. The survival rate to discharge was 13 of 37(35%). A satisfaction survey included 33 neonatal physicians; 32 neonatologists stated the score was easy to comprehend, 26 voted for easy to implement, and 30 voted for ethical relief and moral comfort. CONCLUSIONS: Using a resuscitation score of seven was associated with improved survival until the discharge of those infants resuscitated. NICU physicians described the score as functional and convenient.

Nanoemulsion as a potential ophthalmic delivery system for dorzolamide hydrochloride.

Dilutable nanoemulsions are potent drug delivery vehicles for ophthalmic use due to their numerous advantages as sustained effect and high ability of drug penetration into the deeper layers of the ocular structure and the aqueous humor. The aim of this article was to formulate the antiglaucoma drug dorzolamide hydrochloride as ocular nanoemulsion of high therapeutic efficacy and prolonged effect. Thirty-six systems consisting of different oils, surfactants, and cosurfactants were prepared and their pseudoternary-phase diagrams were constructed by water titration method. Seventeen dorzolamide hydrochloride nanoemulsions were prepared and evaluated for their physicochemical and drug release properties. These nanoemulsions showed acceptable physicochemical properties and exhibited slow drug release. Draize rabbit eye irritation test and histological examination were carried out for those preparations exhibiting superior properties and revealed that they were nonirritant. Biological evaluation of dorzolamide hydrochloride nanoemulsions on normotensive albino rabbits indicated that these products had higher therapeutic efficacy, faster onset of action, and prolonged effect relative to either drug solution or the market product. Formulation of dorzolamide hydrochloride in a nanoemulsion form offers, thus, a more intensive treatment of glaucoma, a decrease in the number of applications per day, and a better patient compliance compared to conventional eye drops.

Design and evaluation of chitosan films for transdermal delivery of glimepiride.

Glimepiride is a third generation oral antidiabetic sulphonylurea drug frequently prescribed to patients of type 2 diabetes. However, its oral therapy is encountered with bioavailability problems due to its poor solubility leading to irreproducible clinical response, in addition to adverse effects like dizziness and gastric disturbances. As a potential for convenient, safe and effective antidiabetic therapy, the rationale of this study was to develop a transdermal delivery system for glimepiride. Chitosan polymer was utilized in developing transdermal films for glimepiride. Chitosan has film forming ability, bioadhesive and absorption enhancing properties. Aiming at optimizing the drug delivery and circumventing the skin barrier function, inclusion complexation of glimepiride with beta-cyclodextrin (beta-CyD) as well as the use of several conventional penetration enhancers were monitored for augmenting the drug flux. The physical and mechanical properties of the prepared films were investigated using tensile testing, IR spectroscopy and X-ray diffractometry. Release studies revealed adequate release rates from chitosan films. Permeation studies through full thickness rat abdominal skin were conducted. High flux values were obtained from films comprising a combination of the drug with limonene and ethanol as well as from films containing glimepiride-beta-CyD complex. In vivo studies on diabetic rats for selected formulae revealed a marked therapeutic efficacy sustained for about 48 hours. The above-mentioned results shed light on feasibility of utilizing chitosan as an effective, safe transdermal delivery system for glimepiride characterized by increased patient compliance and better control of the disease.

Formulation and biological evaluation of glimepiride-cyclodextrin-polymer systems.

Glimepiride is one of the third generation sulfonylureas used for treatment of type 2 diabetes. Poor aqueous solubility and slow dissolution rate of the drug lead to irreproducible clinical response or therapeutic failure in some cases due to subtherapeutic plasma drug levels. Consequently, the rationale of this study was to improve the biological performance of this drug through enhancing its solubility and dissolution rate. Inclusion complexes of glimepiride in beta-cyclodextrin (beta-CyD), hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) and sulfobutylether-beta-cyclodextrin (SBE-beta-CyD), with or without water soluble polymers were prepared by the kneading method. Binary systems were characterized by thermogravimetric analysis, IR spectroscopy and X-ray diffractometry. Phase solubility diagrams revealed increase in solubility of the drug upon cyclodextrin addition, showing A(p) type plot indicating high order complexation. All the ternary systems containing beta-CyD or HP-beta-CyD showed higher dissolution efficiency compared to the corresponding binary systems. The hypoglycemic effect of the most rapidly dissolving ternary system of glimepiride-HP-beta-CyD-PEG 4000 was evaluated after oral administration in diabetic rats by measuring blood glucose levels. The results indicated that this ternary system improves significantly the therapeutic efficacy of the drug. In conclusion, the association of water soluble polymers with glimepiride-CyD systems leads to great enhancement in dissolution rate, increased duration of action and improvement of therapeutic efficacy of the drug.

Implication of inclusion complexation of glimepiride in cyclodextrin-polymer systems on its dissolution, stability and therapeutic efficacy.

The effect of complexation of glimepiride, a poorly water-soluble antidiabetic drug, with beta-cyclodextrin and its derivatives (HP-beta-CyD and SBE-beta-CyD) in presence of different concentrations of water-soluble polymers (HPMC, PVP, PEG 4000 and PEG 6000) on the dissolution rate of the drug has been investigated. The results revealed that the dissolution rate of the drug from these ternary systems is highly dependent on polymer type and concentration. The dissolution rate of the drug from ternary systems containing PEG 4000 or PEG 6000 seems to be generally higher than from systems containing HPMC or PVP. An optimum increase in the dissolution rate of the drug was observed at a polymer concentration of 5% for PEG 4000 or PEG 6000 and at 20% concentration of HPMC or PVP. The dissolution rate of the drug from the ternary system glimepiride-HP-beta-CyD-5% PEG 4000 was high compared to the other systems. Tablets containing the drug or its equivalent amount of this ternary system were prepared and subjected to accelerated stability testing at 40 degrees C/75% R.H. to investigate the effect of storage on the chemical stability as well as therapeutic efficacy of the tablets. The results revealed stability of the tablets and consistent therapeutic efficacy on storage.

A transdermal delivery system for glipizide.

Glipizide is one of the most commonly prescribed drugs for treatment of type 2 diabetes. Oral therapy with glipizide comprises problems of bioavailability fluctuations and may be associated with severe hypoglycaemia and gastric disturbances. As a potential for convenient, safe and effective antidiabetic therapy, the rationale of this study was to develop a transdermal delivery system for glipizide. For this purpose, inclusion complexes of the drug in beta-cyclodextrin (beta-CyD), dimethyl-beta-cyclodextrin (DM-beta-CyD), hydroxypropyl-beta-cyclodextrin (HP-beta-CyD), and hydroxypropyl-gamma-cyclodextrin (HP-gamma-CyD) were prepared. Several percutaneous formulations of the drug and the prepared complexes in different bases (o/w emulsion, polyethylene glycol, carboxymethyl cellulose and Carbopol) were developed. Release studies revealed an improved release of the drug from formulations containing glipizide-CyD complexes. Ex vivo permeation studies through full thickness rat abdominal skin were conducted, whereby the effect of several conventional penetration enhancers (propylene glycol [PG], oleic acid, urea, dimethyl sulfoxide, menthol, limonene and cineole) was monitored. Highest flux was obtained from ointments prepared with Carbopol gel base containing a combination of PG and oleic acid as well as ointments prepared in the same base utilizing glipizide-DM-beta-CyD complex and urea. In vivo studies on diabetic male Wistar rats revealed a marked therapeutic efficacy sustained for about 48 hours. In this respect, two formulations showed best biological performance. In the first formulation, the drug was incorporated in Carbopol gel base in the presence of 20% PG together with 15% oleic acid. The second was prepared by incorporating glipizide-DM-beta-CyD complex in Carbopol gel base in presence of 15% urea. The glucose tolerance test showed suppression of hyperglycaemia induced in glucose-loaded rats. The above-mentioned results might shed a strong beam of light on the feasibility of using glipizide in a transdermal delivery system for treatment of type 2 diabetes with the aim of improving both patient compliance and pathophysiology of the disease.

Effect of early adjunctive use of oral sildenafil and inhaled nitric oxide on the outcome of pulmonary hypertension in newborn infants. A feasibility study.

INTRODUCTION: Inhaled nitric oxide (iNO) is the standard therapy for infants with persistent pulmonary hypertension of the newborn (PPHN). Recently, sildenafil has been evaluated as an alternative or adjunctive pulmonary vasodilator. OBJECTIVE: To assess the effectiveness of adding sildenafil as an early adjunctive therapy together with iNO when treating newborns with PPHN and/or hypoxemic respiratory failure. METHODS: This is a randomized placebo trial on newborns with gestational age > 34 weeks, postnatal age < 48 hours, and diagnosed with PPHN (oxygen index (OI) ≥ 20). Newborns were randomized to two groups: Group A- received oral sildenafil and iNO, and group B- received placebo and iNO. Initial and follow up echocardiography were performed over 14 days period. RESULTS: A total of 24 newborns were recruited; 13 of them received sildenafil in addition to iNO and 11 received iNO and placebo. The most common causes of PPHN were meconium aspiration syndrome, pneumonia, and RDS. At the starting point, OI was marginally higher in the intervention group without statistical significance (29 vs 28). There were no differences between the two groups regarding surfactant administration, incidence of pneumothoraces, and the underlying causes of PPHN. Sildenafil or placebo treatment started within 12 hours after starting iNO (8 vs 6 hours). CONCLUSION: Early use of oral sildenafil next to iNO in cases of PPHN was tolerated well by newborns and it did not show significant adverse effects. Further studies with a larger sample size is needed to assess its effecacy.

Diversity of Bacillus thuringiensis isolates from Egyptian soils as shown by molecular characterization.

Different techniques were adopted for molecular characterization of several indigenous strains of Bacillus thuringiensis (Bt) previously isolated from Egyptian soil samples. These isolates show different toxicity levels against neonate larvae of both insect species; Spodoptera littoralis (Biosduval); and Helicoverpa armigera (Hübner). The parasporal crystals among the most potent isolates contained polypeptides of about 127 and 130 kDa. PCR screening for genes encoding different Cry genes was performed. The Cry 1 gene is the most abundant in these isolates (83.33%) among tested Cry-type genes, followed by Cry 1 gene subfamilies (Cry 1B and Cry 1C) with percentage of 38.88% and 77.77%, respectively. The tested isolates showed the presence of Cry 2A(a,b) gene, but not all of these isolates were positive for Cry 2 gene (55.55%). Only 27.77% and 16.66% of the tested isolates harbor Cry 4 and Cry 3 genes, respectively. All strains were negative in PCR assays for the Vip 3Aa1 gene. Moreover, DNA fingerprinting using RAPD-PCR was performed to detect the genetic similarities and dissimilarities among the different isolates and standard strains. Assessment of Bt diversity based on the combined analysis of their protein and RAPD-PCR banding patterns was performed. This study demonstrates that Bt strains isolated from Egyptian soil samples can be distinguished and identified on the basis of the distribution of Cry-type genes and RAPD fingerprints.

Histopathology of the larval midgut of Helicoverpa armigera (Hübner) fed on Bacillus thuringiensis crystals and Bt-tomato plants.

The histopathological effects of the spore-crystal complex of indigenous Bacillus thuringiensis (Bt) isolate, as well as Cry 2Ab gene expressed in transgenic tomato plants on the midgut of 4th instar larva of Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidea) has been investigated using the transmission electron microscope (TEM). Remarkable ultrastructural changes were observed in the columnar and goblet cells of the larval midgut after feeding on either transgenic tomato leaves, or spore-crystal complex of Bt. The effects observed included breakdown of microvilli of epithelial cells, increase in the electron density of the cytoplasm and vacuolation associated with different sizes of lysosomes; interruption of the goblet cells and distorted goblet cavities which lost their cytoplasmic projections; destruction of the mitochondria which lost their cristae; degeneration of the endoplasmic reticulum; collapse of the nucleus associated with rupture of nuclear envelope and clumped chromatin. Feeding the larvae on transgenic Bt-tomato plants caused in addition to the aforementioned changes severe vacuolation and degeneration of the nucleus in both columnar and goblet cells and the nuclear membrane was broken into electron dense ring spheres.

E1B-deleted adenovirus (dl1520) gene therapy for patients with primary and secondary liver tumors.

Clinical studies were performed with a recombinant mutant adenovirus with an E1B 55-kDa deletion, dl1520, to assess its toxicity and efficacy in patients with irresectable primary and secondary liver tumors. A phase I study showed that dl1520 was well tolerated when administered directly intratumorally, intraarterially, or intravenously up to a dose of 3 x 10(11) PFU. Ultrastructural examination of tissue showed the presence of adenovirus in cell cytoplasm around the nucleus and revealed two dissimilar end points of cell death after virus infection: a preapoptotic sequence and necrosis. A phase II study showed that the combination of dl1520 and 5-fluorouracil (5-FU), when infused into the hepatic artery, was well tolerated. Further improvement in the recombinant vector design will be needed in order to achieve better clinical response.

High seroprevalence of hepatitis C infection among risk groups in Egypt.

High prevalence rates of hepatitis C virus (HCV) were recently reported among Egyptian blood donors. To confirm these observations and estimate the magnitude of HCV infection in this country, we determined the prevalence of antibodies to HCV (anti-HCV) in samples collected in 1992 from seven different populations of children and adults living in Egypt. Anti-HCV was found in 12.1% of rural primary schoolchildren, 18.1% of residents of a rural village, 22.1% of army recruits, 16.4% of children with hepatosplenomegaly, 54.9% of hospitalized, multitransfused children, 46.2% of adults on hemodialysis, and 47.2% of adults with chronic liver disease or hepatoma. Age-related prevalence of anti-HCV in a random sample of 270 inhabitants of a rural village increased progressively from zero in those 5-10 years of age to 41% in adults greater than the age of 50. Although the increased prevalence of anti-HCV among children and adults with parenteral exposures and chronic liver disease was expected, the prevalence of anti-HCV among persons representing the general population of Egypt was strikingly high. These data demonstrate the magnitude of HCV infection and its importance in chronic liver disease in Egypt. Future studies are needed to determine the routes of transmission of HCV in this country.

Short-term healing of autogenous and allogeneic bone grafts after sinus augmentation: a report of 2 cases.

Sinus augmentation to facilitate the placement of cylindrical endosseous implants in the posterior maxilla has become more commonplace, and many different materials have been used for the sinus graft. The results of two sinus augmentation procedures, one grafted with demineralized freeze-dried bone (DFDB) and the other with autogenous iliac bone, are presented. Bone cores were obtained with a trephine drill from the grafted regions at the time of implant placement. Eight implants were placed into the grafted areas in each subject. The sample from the sinus grafted with autogenous bone was obtained 8 months postoperatively and the bone core from the sinus grafted with DFDB was taken 16 months postoperatively. The bone specimens were subsequently examined under light microscopy. The autogenous specimens demonstrated new bone formation with increased quantity and improved quality when compared to the specimens obtained from the sites grafted with allogeneic bone. All 8 implants placed into the autogenous grafts were clinically osseointegrated at stage 2. At 16-months postsurgery, the bone core taken from the site grafted with DFDB demonstrated poor bone quality and still contained remnants of the graft material in the region approximating the sinus membrane. Two of the 8 implants placed into the allogeneic grafts failed at stage 2. These findings suggest that autogenous sinus grafts produce bone of adequate quantity and quality for implant placement, whereas DFDB sinus grafts are not completely remodeled by the host and may produce bone of insufficient quality and quantity for predictable implant placement.