Arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: a single center experience

Arsenic trioxide (As(2)O(3)) has been found effective in the treatment in the treatment of acute promyelocytic leukemia (APML). Most studies with As(2)O(3) involve patients with APML who have relapsed following standard therapy. Between January 1998 and July 2000, 14 patients were recruited for an ongoing trial of As(2)O(3) in the treatment of newly diagnosed APML. Arsenic trioxide was administered at a dose of 10 mg/day until complete remission (CR) was achieved. Afterward, a consolidation course and a maintenance schedule consisting of As(2)O(3) as a single agent were administered over 6 months. There were 3 early deaths related to intra-cerebral hemorrhage: two on day 3 and one on day 4. Of the 11 evaluable patients, one died on day 21 secondary to uncontrolled sepsis, while the remaining 10 (91%) have attained CR. The average time to CR was 52.3 days (range: 34-70 days). One patient developed an isolated central nervous system (CNS) relapse and subsequently went into a second CR following therapy with triple intrathecal chemotherapy, cranial irradiation, and an additional 4-week course of systemic As(2)O(3). This patient, as well as the remaining nine, has continued to remain in CR at a median follow up of 15 months (range: 2-33 months). Eight out of 10 patients achieved molecular remission at variable periods during their consolidation and maintenance schedules. One patient developed an ATRA syndrome and was administered daunorubicin (40 mg/day) for 2 days. The side effects with this therapy were minimal and did not require cessation of therapy in any patient. There was no significant hepatic toxicity. In our experience, arsenic trioxide is effective in inducing and maintaining remission in patients with APML with minimal side effects. The optimal regimen and total dose required need to be defined.     

Radiation exposure impairs luteinizing hormone signal transduction and steroidogenesis in cultured human leydig cells.

Therapeutic, accidental, and experimental radiation exposures decreased serum testosterone in males, leading to various sexual problems. Since testicular Leydig cells are the predominant source of circulating testosterone, findings on the direct effects of radiation on Leydig cell steroidogenesis and the mechanism behind such effects would be of greater importance to the use of safer radiation doses in cancer therapy and to adopt preventive or therapeutic measures to alleviate postirradiation lesions, respectively. Therefore, this study was undertaken to explore the same using cultured human Leydig cells. Testicles removed from advanced prostatic carcinoma patients were used for isolation and purification of Leydig cells. Purified Leydig cells were cultured and then exposed to different doses (2, 4, 6, 8, and 10 Gy) of fractioned gamma radiation. Normal and irradiated cells were used for luteinizing hormone (LH) receptor quantification or total RNA isolation to study LH receptor mRNA expression or LH/cyclic AMP (cAMP) stimulation test. While LH-stimulated cells were used for cAMP assay, LH- and cAMP-stimulated cells were used for the estimation of steroidogenic enzymes, testosterone and estradiol production. Radiation exposure caused adverse effects on Leydig cell steroidogenesis in a dose-dependent manner. While lower doses (2 and 4 Gy) were ineffective, higher doses (6 Gy and above) drastically decreased LH receptor, basal and LH-stimulated cAMP generation, and basal, LH-, and cAMP-stimulated steroidogenesis. While 2 Gy of radiation exposure increased the LH receptor mRNA level, other doses did not induce any significant change. Therefore, it is concluded that higher doses of radiation impair Leydig cell steroidogenesis by affecting LH signal transduction at the level of both pre- and post-cAMP generation. Decreased level of LH receptors following higher doses of radiation exposure is not coupled with impaired expression of its mRNA.     

Role of massage therapy on reduction of neonatal hyperbilirubinemia in term and preterm neonates: a review of clinical trials

Background: Neonatal hyperbilirubinemia (NNH) is one of the leading causes of admissions in nursery throughout the world. It affects approximately 2.4–15% of neonates during the first 2 weeks of life.

Aims: To evaluate the role of massage therapy for reduction of NNH in both term and preterm neonates.

Method: The literature search was done for various randomized control trials (RCTs) by searching the Cochrane Library, PubMed, and EMBASE.

Results: This review included total of 10 RCTs (two in preterm neonates and eight in term neonates) that fulfilled inclusion criteria. In most of the trials, Field massage was given. Six out of eight trials reported reduction in bilirubin levels in term neonates. However, only one trial (out of two) reported significant reduction in bilirubin levels in preterm neonates. Both trials in preterm neonates and most of the trials in term neonates (five trials) reported increased stool frequencies.

Conclusion: Role of massage therapy in the management of NNH is supported by the current evidence. However, due to limitations of the trials, current evidences are not sufficient to use massage therapy for the management of NNH in routine practice.     

An Analysis of Popular Online Erectile Dysfunction Supplements

IntroductionErectile dysfunction supplements (ED-Ss) are featured on online marketplaces like Amazon.com, with dedicated pages and claims that they naturally treat ED. However, their efficacy and safety are largely unknown, limiting the ability to counsel patients regarding their use.AimTo evaluate the highest rated and most frequently reviewed ED-Ss on Amazon.com to facilitate patient counseling regarding marketing myths, ingredient profiles, and evidence for product efficacy and safety.MethodsThe Amazon marketplace was queried using the key term “erectile dysfunction” with default search settings and ranking items based on relevance. The top 6 ED-S products identified on September 29, 2018, were reviewed based on price, ratings, reviews, manufacturer, and ingredients. Consumer reviews were categorized using subtopics within the International Index of Erectile Function (IIEF) questionnaire to better understand ED-S efficacy and then reanalyzed following filtration of untrustworthy comments using ReviewMeta.com, a proprietary Amazon review analysis software.OutcomesQuantitative and qualitative evaluation of ED-S products sold on Amazon.com.ResultsThe top 6 ED-Ss had an average of 2,121 ± 1,282 reviews and a mean rating of 3.92 ± 0.42 stars. A total of 21 ingredients were identified in these ED-Ss. Ginseng, horny goat weed, L-arginine, and tongkat ali were the most popular ingredients included in the analyzed products. Our literature review identified 413 studies involving the 21 identified ingredients, of which 59 (16%) involved human subjects. Among these 69 human studies, only 12 (17%) investigated supplement ingredients individually and reported improvement in ED. Analysis of top-ranked customer reviews from the first 2 pages of reviews for each supplement revealed differences in IIEF scores before and after ReviewMeta.com filtration. After filtration, we observed a 77% decrease in reviews reporting improved erection strength, an 83% decrease in reviews reporting improved ability to maintain erection, a 90% decrease in reviews reporting increased sexual satisfaction, an 88% decrease in reviews reporting increased enjoyment with intercourse, and an 89% decrease in reviews reporting increased erection confidence.Strengths & LimitationsStudy strengths include a novel approach to ascertaining consumers’ perceptions and satisfaction with ED-Ss and practical summary information that clinicians can provide to patients. Limitations include selection bias, the small number of supplements analyzed, and the proprietary nature of the Amazon review analysis software.ConclusionsOur investigation revealed that human studies evaluating the efficacy of ED-S ingredients are limited and have yielded no definitive findings of the effects on ED. Patients considering ED-S use should receive appropriate counseling, given the prevalence of disingenuous reviews and the ready availability of Food and Drug Administration–approved drug therapies.Balasubramanian A, Thirumavalavan N, Srivatsav A, et al. An Analysis of Popular Online Erectile Dysfunction Supplements. J Sex Med 2019;16:843–852.     

STEREOCHEMICAL CRITERIA FOR POLYPEPTIDE AND PROTEIN CHAIN CONFORMATIONS.

As a first step in the study of the effect of the distortions of the angle NC^aC' (τ) at the α-carbon atom and the planarity of the peptide unit (measured by parameter ω) on the steric map of two linked peptide units, these distortions have been analysed from known crystal structure data on amino acids, peptides and the globular proteins, myoglobin, lysozyme, α-chymotrypsin, carboxypeptidase-A, and ribonuclease-S. Corresponding to three different values each of τ and ω around the ideal values (of 110° and 180° respectively) the contact maps are drawn. Most of the observed conformations of non-glycyl residues in the globular proteins are found to be within the allowed regions. The 3 → 1 type of N-H. O = C hydrogen bond between adjacent units is considered and the possibility of the formation of this hydrogen bond around φ= +90° and φ = -90° (leading to a left-handed helix, if continued) is explored in more detail. The conformations at some of the residues in α-chymotrypsin and carboxypeptidase-A are shown to form the right-handed 3 → 1 type of hydrogen bonds.     

Modulation of vascular remodeling induced by a brief intraluminal exposure to the recombinant R7020 strain of Herpes simplex-1

OBJECTIVE: Vascular remodeling in response to injury or low shear stress (or both) is characterized by neointimal hyperplasia and luminal contraction. When profound, the response leads to restenosis after percutaneous endovascular intervention as well as to de novo stenosis in vein grafts. It has recently been reported that exposure of vein patches to neurovirulence-attenuated Herpes simplex virus-1 (HSV-1) decreases neointimal hyperplasia and increases luminal area. This experiment tested the hypothesis that R7020, a more highly attenuated mutant of HSV-1, would modulate the vascular remodeling response of experimental vein grafts chronically exposed to low shear stress. METHODS: The external jugular veins of 31 New Zealand white rabbits were clamped and intraluminally exposed to vehicle (phospate-buffered saline solution, n = 11), R7020 2.5 x 10(8) plaque forming units [PFU]/mL (n = 8), or R7020 2.5 x 10(9) PFU/mL (n = 12) for 10 or 30 minutes at an average pressure of 80 mm Hg. After exposure, an end-to-side distal external jugular-to-common carotid artery anastomosis was created, resulting in a widely patent arteriovenous fistula. The external jugular was suture-ligated just proximal to the thoracic inlet, distal to a small 10- to 50-microm venous tributary, creating a reversed vein "graft" segment immediately and abruptly exposed to arterial pressure (48 +/- 3 mm Hg) and low shear stress (0.12 +/- .02 dyne/cm(2)). In the 29 animals (N = 31) that survived to harvest, 26 grafts were found to be patent and were analyzed further. Nine grafts were harvested within the first week after operation, snap frozen in liquid nitrogen, and assayed for the presence of the Herpes viral immediate-response protein ICP0 by Western blot analysis. The 17 remaining grafts were perfusion-fixed, excised, stained, and analyzed morphometrically by digital planimetry. RESULTS: In patent grafts, the hemodynamic environment of low shear stress was maintained (shear stress at harvest, 0.26 +/- .06 dyne/cm(2)). Western blot analysis revealed the presence of ICP0 in R7020-exposed vein grafts after 2, 3, 7, and 14 days; ICP0 was not detected in unexposed vein grafts or adjacent carotid arteries. After 4 weeks, vein grafts exposed to R7020 exhibited a statistically significantly increased ratio of luminal radius to wall thickness, indicating altered remodeling (vehicle, 6.7 +/- 1.3; R7020 2.5 x 10(8), 9.1 +/- 1.3; R7020 2.5 x 10(9) ratio, 11.3 +/- 1.4; P < .05 for high dose compared with vehicle). CONCLUSION: A brief exposure of the neurovirulence-attenuated HSV-1 strain R7020 results in an increased ratio of luminal radius to wall thickness in experimental vein grafts chronically exposed to low shear stress.