Systematic Review of Potential Health Risks Posed by Pharmaceutical, Occupational and Consumer Exposures to Metallic and Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide and Its Soluble Salts

Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007). Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of “total Al”assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al+ 3 to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)+ 2 and Al(H2O)6 + 3] that after complexation with O2•−, generate Al superoxides [Al(O2•)](H2O5)]+ 2. Semireduced AlO2• radicals deplete mitochondrial Fe and promote generation of H2O2, O2 • − and OH•. Thus, it is the Al+ 3-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer\u27s disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances

Analysis of Neonatal Sepsis in Kumasi, Ghana Through Paper-Based Medical Records

Reducing infant mortality is Millennium Development Goal 4 in Ghana, though it has remained high and unchanged. Improving care and reducing health complications related to infections and respiratory distress has shown to decrease the prevalence of neonatal deaths and preterm births. The objective of this study is to present data originating from an electronic medical records (EMR) pilot project and communicate the results of an analysis of neonatal sepsis using health information from paper-based medical records to identify characteristics of the neonatal patients at the Komfo Anokye Teaching Hospital in Kumasi, Ghana. Medical records from the Mother Baby Ward (n=198) from 2009-2014 were processed using scanners connected to laptop computers. Health information was manually extracted and verified by two researchers for quality assurance purposes and included sepsis, respiratory distress, cough, difficulty feeding, lethargy, seizures, jaundice, birth history, birth maturity and birth location. Regression analysis revealed a significant association between sepsis and birth location (p=0.0180, 95% CI) as well as sepsis and jaundice (p=0.0446, 95% CI). A descriptive profile of the population revealed that 63.6% of infants comprised of 97 males and 101 females were differentially diagnosed as having sepsis. There were 21 (10%) twins observed. Of the 198 cases included in the analysis, there were 127 (64%) full-term births, 105 (53%) cases reporting respiratory distress and 93 (46%) reporting jaundice. The process of manually scanning and converting paper-based medical records to later use for manual data extraction provides a safe and secure way to evaluate health information related to infant and neonate health

Lipid associated antioxidants: arylesterase and paraoxonase-1 in benign prostatic hyperplasia treatment-naïve patients

Background: Oxidative stress and antioxidants have been implicated in many diseases including prostate cancer and benign prostatic hyperplasia (BPH). Lipid peroxidation contributes to oxidative stress. However, new and emerging antioxidants such as paraoxonase 1 (PON1) and arylesterase (ARE) associated with lipoprotein peroxidation have not been examined in BPH patients. PON1 and ARE, a high-density lipoprotein (HDL) cholesterol-bound enzyme system of antioxidants, protect low-density lipoprotein (LDL) cholesterol and HDL from oxidation by hydrolysis. The study primarily determined paraoxonase (PON1) and ARE activities in BPH treatment-naïve patients. Materials and methods: Sixty newly diagnosed patients (treatment-naïve) alongside 30 apparently healthy controls were recruited. Blood examinations included lipid profile (total cholesterol, triglycerides, LDL, HDL), glutathione peroxidase, PON1, ARE, and prostate specific antigen (PSA). Prostate volume and International Prostate Symptoms Score (IPSS) were determined. Results: PSA was significantly different between patient and control groups (P  0.05), ARE was significantly lower in the patient group (61.31 ± 21.76/49.30 ± 19.82 ng/mL; P = 0.0098). No correlation was established between antioxidants and the lipid profile except for the LDL and PON1 patient group (r = 0.1486, P = 0.0374). Similarly, a weak correlation was also established between PSA and LDL in the patient group (r = –0.275, P = 0.033). PON1/HDL ratio was not significantly different. However, the ARE/HDL ratio was significantly lower in the patient group (P < 0.0001). Conclusion: These results signify the presence of a higher lipoprotein peroxidation activity and lower lipid-associated antioxidant activity in the patient group. The ARE/HDL ratio is a better indicator of the HDL associated antioxidant than the PON1/HDL ratio or the individual antioxidants (PON1 and ARE) as reported by others

Endogenous Sphingolipid Signaling Pathway Implicated in the Action of Croton membranaceus on the Prostate Gland in BPH Patients

Background: Croton membranaceus extract has apoptotic effects on BPH-1 cells. This study determined if the apoptotic effects were created through the ceramide pathway. Methods: The study was a follow-up to a previous observational study of 30 histologically confirmed patients with benign prostatic hyperplasia (BPH) who were on C. membranaceus ethanolic extract at 20 mg t.i.d orally for 3 mo. Thereafter, total and free prostate-specific antigen (PSA), lipid profile plus Apo lipoprotein A and B, ceramide/Sphingophospho-kinase 1 (SphK1) and 2 (SphK2), sphingosine lyase (SPL), the cytotoxic adducts of oxidative stress 4-hydroxy-2-nonenal (4HNE) and malondialdehyde (MDA), were determined. Results: Total and free PSA were significantly (p &lt; 0.05) different after treatment. Apo lipoprotein A was significantly different (p = 0.024). The SphK1/SphK2 ratio reduced significantly (p = 0.049). Furthermore, SPL, ceramide, and MDA increased significantly after treatment (p = 0.05, p = 0.004, and p = 0.007, respectively). A weak positive correlation was found between high-density lipoprotein (HDL) cholesterol and SphK1, and HDL and ceramide before treatment (p = 0.036, r = 0.3826; p = 0.018, r = 0.4286, respectively. Conclusions: C. membranaceus uses the ceramide pathway by modulating the SphK1/SphK2 ratio and increasing SPL to generate oxidative stress and consequently apoptosis