Disruption of PPT1 or PPT2 causes neuronal ceroid lipofuscinosis in knockout mice

PPT1 and PPT2 encode two lysosomal thioesterases that catalyze the hydrolysis of long chain fatty acyl CoAs. In addition to this function, PPT1 (palmitoyl-protein thioesterase 1) hydrolyzes fatty acids from modified cysteine residues in proteins that are undergoing degradation in the lysosome. PPT1 deficiency in humans causes a neurodegenerative disorder, infantile neuronal ceroid lipofuscinosis (also known as infantile Batten disease). In the current work, we engineered disruptions in the PPT1 and PPT2 genes to create "knockout" mice that were deficient in either enzyme. Both lines of mice were viable and fertile. However, both lines developed spasticity (a "clasping" phenotype) at a median age of 21 wk and 29 wk, respectively. Motor abnormalities progressed in the PPT1 knockout mice, leading to death by 10 mo of age. In contrast, the majority of PPT2 mice were alive at 12 mo. Myoclonic jerking and seizures were prominent in the PPT1 mice. Autofluorescent storage material was striking throughout the brains of both strains of mice. Neuronal loss and apoptosis were particularly prominent in PPT1-deficient brains. These studies provide a mouse model for infantile neuronal ceroid lipofuscinosis and further suggest that PPT2 serves a role in the brain that is not carried out by PPT1.     

Hepatic involvement in patients with human immunodeficiency virus infection: discrepancies between AIDS patients and those with earlier stages of infection

The effect of human immunodeficiency virus (HIV) infection on type and severity of liver disease was studied in 61 HIV-positive patients who did not have AIDS and in 45 AIDS patients. Liver biopsies revealed viral hepatitis in 12 of 18 non-AIDS patients but in only 4 of 34 AIDS patients (P less than .0005, Fisher's exact test). Acute, non-A non-B, and chronic active hepatitis B were seen exclusively in the non-AIDS group; however, chronic persistent hepatitis B was seen in both groups. In 9 of 18 AIDS patients intra vitam liver histopathology established diagnoses of opportunistic infections or tumors. Tissue reaction to certain pathogens, such as hepatitis B virus, mycobacteria, and cryptococci, seems to be milder in AIDS patients than in others who are HIV positive or the expected reaction of the normal host. This is likely because of impaired cell-mediated immunity in patients with advanced HIV disease.     

Bone condition of the maxillary zygomatic process prior to orthodontic anchorage plate fixation

Journal of Orofacial Orthopedics / Fortschritte der Kieferorthopädie - The clinical success of orthodontic miniplates depends on the stability of the miniscrews used for fixation. For good...     

Frailty in Heart Failure

Considering the increasing age of individuals affected with heart failure (HF), a specific approach to their treatment is required, with more attention paid to geriatric conditions such as poor mobility, multiple disabilities, and cognitive impairment. Frailty is a distinct biological syndrome reflecting decreased physiologic reserve and resistance to stressors. It was shown to occur frequently in patients with heart failure, with the prevalence ranging from 15 to 74 %, depending on the studied population and the method of assessment. We reviewed literature data on the influence of frailty, skeletal abnormalities, comorbidities and geriatric condition on diagnosis, treatment, and outcomes in elderly patients with HF. Identification of frailty in patients with HF is important from the clinical point of view, as this condition exerts unfavorable effects on the course of heart failure. Frailty contributes to a higher frequency of visits to emergency departments, hospitalizations, and mortality in patients with HF. Exercise may improve mobility, and nursing support can be implemented to help the patients adhere to medications. Therefore, frail patients should be diagnosed and treated according to available guidelines, and successfully educated about their condition.     

The Last Mile: Translational Research to Improve CKD Outcomes

The National Institute of Diabetes and Digestive and Kidney Diseases–supported Kidney Research National Dialogue asked the scientific community to formulate and prioritize research objectives that would enhance understanding of kidney function and disease and improve clinical outcomes. An engaged and growing group of investigators working in type 2 translation (from clinical evidence to implementation in the community) identified barriers to improving patient care in CKD and suggested research priorities to test translational strategies that have been effective for other chronic diseases.