Study of chimerism in long-term survivors after bone marrow transplantation for severe acquired aplastic anemia

Chimerism studies employing PCR and Southern techniques targeting VNTR loci were performed in 17 severe acquired aplastic anemia patients who were long-term survivors after BMT. They were studied a median of 4 years after BMT (1-12). All patients had normal blood counts. All patients conditioned with radiation-based schemes showed a full donor pattern of hemopoiesis. Conversely, out of five patients who received only cyclophosphamide as conditioning therapy, two of them had a late graft failure (2.4 and 3 years after BMT). One of these relapsing patients had a durable mixed chimerism, which was first detected 1 month after BMT. Our results seem to suggest that durable mixed chimerism can antecede graft failure in some patients conditioned only with cyclophosphamide, and that a more stringent monitoring can be clinically rewarding in this group of patients.     

Male pseudohermaphroditism caused by enzymatic deficiency of 17-alpha-hydroxylase. 1st case reported in Puerto Rico

A 36 year old white female came to our service after having been evaluated on repetitive occasions in the past for a workup of gigantism and acromegalic features. Since childhood she had developed tall stature, frontal bossing, prominence of zygomatic bones, separated teeth, large hands and size 14 shoes. Human growth hormone and somatomedin serum levels had been normal on all occasions tested. Her past history was significant for primary amenorrhea and a 12 year history of hypertension. On physical examination BP was 140/100, height 6' 2", weight 2571 bs. Her phenotype was truly acromegalic. There was absence of axillary and pubic hair with no breast development. External genitalia was of female appearance. Laboratory evaluation showed increased FSH of 88 mlU/ml, increase LH of 65.6 mlU/ml and decreased E2 of 12.6 pg/ml. Other findings were low serum cortisol of 0.2 mg/dl, high ACTH of 344 pg/ml, low 17-Ketosteroids, high pregnenolone levels of 595 mg/dl, low 17-hydroxypregnenolone less than 10 ng/dl, very high aldosterone of 31 ng/dl and suppressed PRA of less than 0.1 ng/ml. A pelvic sonogram showed a right ovoid structure which could represent a gonad and failed to identify the uterus and left gonad. A bone densitometry showed a decrease bone mineral density compatible with osteoporosis. Chromosome study showed a karyotype of 46-XY. A diagnosis was made of congenital adrenal hyperplasia secondary to 17-alpha-hydroxylase deficiency in a genotypic male. Our patient was referred to the department of gynecology for surgical removal of the gonads. It is amazing how a patient with severe adrenal insufficiency can withstand 36 years of her life undiagnosed without going into an adrenal crisis. Her tall stature and acromegalic features were the striking signs confusing all physicians and delaying the correct diagnosis and appropriate treatment. There has been reported worldwide, nearly 120 cases with documented severe 17-alpha-hydroxylase deficiency. To our knowledge this is the first case identified in Puerto Rico of male pseudohermaphroditism secondary to 17-alpha-hydroxylase enzyme deficiency.     

Mechanical behavior and failure analysis of recycled polymers by use of miniature punch specimens

In today's society, recycling is a priority, and using recycled materials to obtain new 100% reusable materials is an important aspect of some manufacturing sectors. Clearly, the mechanical properties of these new materials can vary considerably from the original material, so it is necessary to carry out a complete mechanical characterization to know its behavior for both standard specimens and final components. One of the common drawbacks is the inability to extract standard size specimens from a final component with a reduced size. In this paper, the use of the small punch test is proposed as a means of solving this problem. At present, this test is used for estimating mechanical properties in those cases when there is not a sufficient amount of material to perform standard tests. The main purpose of this paper is to analyse the feasibility of using miniature punch specimens for the mechanical characterization of recycled polymers. The results are compared with those obtained from standard uniaxial tensile specimens, and a corresponding correlation between the two tests is established. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 42911.     

Evaluation of lipase from Burkholderia cepacia immobilized in alginate beads and application in the synthesis of banana flavor (isoamyl acetate)

The alginate in bead forms was used to immobilize Burkholderia cepacia lipase. The microencapsulation technique for lipase entrapment was a 2% (w/v) of sodium alginate concentration prepared by ionic gelation using calcium chloride as the cross-linking agent in a gelling solution. The beads were tested in different solvents as acetone, chloroform, toluene, n-hexane, and n-heptane. Over a 5-day period (120?h), the n-heptane maintained the reasonable (excellent) residual activity of the immobilized lipase. Morphological studies on reused beads and new beads were performed. All beads for isoamyl acetate yield were tested. The reused bead leaches substantially, with a maximum ester yield of 92%. With modifications in the molar ratios, the synthesis of banana flavor (isoamyl acetate) was performed in both the alcohol per acid and acid per alcohol excesses.     

Phenolic diterpene and α‐tocopherol contents in leaf extracts of 60 Salvia species

BACKGROUND: Carnosic acid and carnosol, the two major phenolic diterpenes present in rosemary and sage extracts, have received attention in food science and biomedicine because of their potent antioxidant properties. In plants, these compounds have been identified as being present in some species of the family Lamiaceae, but there is still little information about their distribution within the plant kingdom. The aim of the present study was to gain a better understanding of the occurrence of these compounds within leaf extracts of the genus Salvia and also to examine to what extent leaf senescence may influence their accumulation in relation to that of α‐tocopherol (vitamin E). RESULTS: Methanolic leaf extracts of 60 species of the genus Salvia were tested for the presence of carnosic acid and carnosol. These two diterpenes were detected in 48 and 27 species respectively. In contrast, α‐tocopherol was present in all species examined. Leaf senescence in Salvia officinalis resulted in α‐tocopherol increases by up to 5.5‐fold, while carnosic acid and carnosol increased by up to 18 and 290% respectively. Isorosmanol, an oxidation product of carnosic acid, increased by up to 2.1‐fold in senescing leaves. CONCLUSION: It was found that, while α‐tocopherol is ubiquitous in the genus Salvia, phenolic diterpenes are present in several but not all species. It was also shown that leaf senescence may increase the yield of both phenolic diterpenes and α‐tocopherol in sage extracts. Copyright © 2008 Society of Chemical Industry     

A medicinal-chemistry-guided approach to selective and druglike sigma 1 ligands

Based on a medicinal-chemistry-guided approach, three novel series of druglike cycloalkyl-annelated pyrazoles were synthesized and display high affinity (pKi>8) for the sigma1 receptor. Structure-affinity relationships were established, and the different scaffolds were optimized with respect to sigma1 binding and selectivity versus the sigma2 receptor and the hERG channel, resulting in selective compounds that have Ki values (for sigma1) in the subnanomolar range. Selected compounds were screened for cytochrome P450 inhibition (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4), metabolic stability (rat and human liver microsomes), and cell-membrane permeability (Caco-2). They showed favorable in vitro ADME properties as well as favorable calculated druglike and experimental physicochemical properties. Furthermore, compounds 7 f and 17 a, for example, displayed high selectivity (affinity) for the sigma1 receptor against a wide range of other receptors (>60). With these valuable tool compounds in hand, we are further exploring the role of the sigma1 receptor in relevant animal models corresponding to such medicinal indications as drug abuse, pain, depression, anxiety, and psychosis.     

Gastrointestinal tolerability of meloxicam compared to diclofenac in osteoarthritis patients. International MELISSA Study Group. Meloxicam Large-scale International Study Safety Assessment

Although widely used, non-steroidal anti-inflammatory drugs (NSAIDs) are associated with a high incidence of gastrointestinal (GI) side-effects. Inhibition of the cyclooxygenase (COX) enzyme is the basis for both the efficacy and toxicity of NSAIDs. The discovery of two COX isoforms, constitutive COX-1 and inducible COX-2, has led to the hypothesis that selective inhibition of COX-2 will minimize the potential for GI toxicity without compromising efficacy. The Meloxicam Large-scale International Study Safety Assessment (MELISSA) trial reported here was therefore set up to investigate the tolerability of meloxicam, a preferential inhibitor of COX-2, compared to diclofenac. MELISSA was a large-scale, double-blind, randomized, international, prospective trial, conducted over 28 days in patients with symptomatic osteoarthritis. Patients received either meloxicam 7.5 mg or diclofenac 100 mg slow release, the recommended doses for the treatment of osteoarthritis. Evaluation of the profile of adverse events was the main aim of the trial, together with assessment of efficacy. A total of 9323 patients received treatment (4635 and 4688 in the meloxicam and diclofenac groups, respectively). Significantly fewer adverse events were reported by patients receiving meloxicam. This was attributable to fewer GI adverse events (13%) compared to diclofenac (19%; P < 0.001). Of the most common GI adverse events, there was significantly less dyspepsia (P < 0.001), nausea and vomiting (P < 0.05), abdominal pain (P < 0.001) and diarrhoea (P < 0.001) with meloxicam compared to diclofenac. Five patients on meloxicam experienced a perforation, ulcer or bleed vs seven on diclofenac (not significant). No endoscopically verified ulcer complication was detected in the meloxicam group compared to four with diclofenac. There were five patient days of hospitalization in patients on meloxicam compared to 121 with diclofenac. Adverse events caused withdrawal from the study in 254 patients receiving meloxicam (5.48%) compared to 373 (7.96%) on diclofenac (P < 0.001). These differences were attributable to differences in reported GI adverse events (3.02% on meloxicam vs 6.14% on diclofenac; P < 0.001). Differences in efficacy, as assessed by visual analogue scales, consistently favoured diclofenac. In all instances, 95% confidence intervals did not cross zero, suggesting a statistically significant effect. However, differences were small (4.5-9.01% difference) and did not reach pre-determined levels of clinical significance. Nevertheless, significantly more patients discontinued meloxicam because of lack of efficacy (80 out of 4635 vs 49 out of 4688; P < 0.01). The MELISSA trial confirms earlier studies suggesting that meloxicam has a significantly improved GI tolerability profile in comparison with other NSAIDs, including diclofenac. These results may in part reflect the preferential COX-2 selectivity of meloxicam, although the dose and other aspects of tolerability may be important. These results may provide support for the hypothesis that selective inhibition of COX-2 relative to COX-1 might be an effective approach towards improved NSAID therapy.     

Mucocutaneous manifestations in acute HIV infection. 3 case reports

We report three patients who developed a generalized rash with oral, genital or perianal ulcerations as a result of acute infection due to HIV. The primary infection was diagnosed by seroconversion (by means of EIA and Western blot techniques). Definitive diagnosis was established on days 52, 85 and 97 after the appearance of the rash. The p24 protein of the HIV was only detected in the early phase of the disorder in the two cases in which this study was carried out.     

Fast-response low-ripple envelope follower

A novel envelope detector structure is proposed in this paper that overcomes the traditional trade-off required in these circuits. It improves both the tracking and keeping of the signal and thereby obtains great savings of capacitor area. At the same time, it cancels nonlinearities due to the use of switches when this technique is employed, such as nonlinearities caused by charge injection and, tenders high performance with small ripple (<1%), fast settling (0.4 μs) and high linearity.