How to take arms against central apneas in heart failure

Introduction Despite being a risk mediator in several observational studies, central apneas are currently orphan of treatment in heart failure. After the neutral effects on survival of two randomized controlled trials (RCTs) based on the use of positive airway pressure (the CANPAP and SERVE-HF trials), two alternative hypotheses have been formulated:

1) Periodic breathing/Cheyne-Stokes respiration (PB/CSR) in HF is protective. Indeed, the Naughton’s hypothesis assumes that hyperventilation leads to increased cardiac output, lung volume, oxygen storage and reduced muscle sympathetic nerve activity, while central apnea to respiratory muscle rest and hypoxia-induced erythropoiesis.

2) The use of positive airway pressure is just a wrong treatment for PB/CSR. If this is the case, the search for novel potential alternative treatment approaches is mandatory in HF.

Areas covered This review will focus on the crucial issue of whether PB/CSR should be treated or not in HF, first by outlining the ideal design of pathophysiological studies to test the Naughton’s hypothesis and second by summarizing the treatment strategies so far proposed for PB/CSR in HF and identifying the most promising options to be tested in future RCTs.

Expert commentary It is likely that PB/CSR may be compensatory in some cases, but after a certain threshold (to be defined) it becomes maladaptive with negative prognostic meaning in HF. The development of a pathophysiologically based treatment targeting feedback resetting and neurohormonal activation underlying PB/CSR is likely to be the best option to obtain survival benefits in HF.     

Keratin films for ocular surface reconstruction

Human amniotic membrane (AM) is frequently used as a substrate for ocular surface reconstruction. Its disadvantages (e.g., reduced transparency and biomechanical strength, heterogeneity depending on donor) create the need for standardized alternatives. Keratin from hair or wool has been proposed as an appropriate material for producing films or cell cultivation scaffolds. The current study was performed to develop transparent, stable and transferable films based on human hair keratin that support cellular adhesion and proliferation. The films were engineered by a multi-step procedure including keratin extraction, neutral and alkaline dialysis, drying and a curing process. Keratin films were investigated by SDS-PAGE, SEM and X-ray analyses. Furthermore, swelling and water absorption of the films were studied, as were tensile strength and light transmission (UV/VIS). Finally, the growth behavior of corneal epithelial cells on the keratin films and AM was estimated in proliferation studies. In addition, we assessed the seeding efficiency and cell detachment behavior during trypsinization. The film-forming process resulted in transparent films composed of nanoparticulate keratin structures. The film characteristics could be varied by changing the protein composition, adding softening agents or varying the curing temperature and duration. Based on these findings, an optimized protocol was developed. The films showed improved light transmission and biomechanical strength in comparison to AM. Furthermore, cell behavior on the films was similar to that found on AM. We conclude that keratin films may represent a new, promising alternative for ocular surface reconstruction.     

Herb–Drug Interactions with St John’s Wort (Hypericum perforatum): an Update on Clinical Observations

St John’s wort (SJW) extracts, prepared from the aerial parts of Hypericum perforatum, contain numerous pharmacologically active ingredients, including naphthodianthrones (e.g., hypericin and its derivatives), phloroglucinols derivatives (e.g., hyperforin, which inhibits the reuptake of a number of neurotransmitters, including serotonin), and flavonoids. Such extracts are widely used for the treatment of mild-to-moderate depression. As a monotherapy, SJW has an encouraging safety profile. However, relevant and, in some case, life-threatening interactions have been reported, particularly with drugs which are substrate of cytochrome P450 and/or P-glycoprotein. Well-documented SJW interactions include (1) reduced blood cyclosporin concentration, as suggested by multiple case reports as well as by clinical trials, (2) serotonin syndrome or lethargy when SJW was given with serotonin reuptake inhibitors, (3) unwanted pregnancies in women while using oral contraceptives and SJW, and (4) reduced plasma drug concentration of antiretroviral (e.g., indinavir, nevirapine) and anticancer (i.e., irinotecan, imatinib) drugs. Hyperforin, which is believed to contribute to the antidepressant action of St John’s wort, is also strongly suspected to be responsible of most of the described interactions.     

Peripheral endocannabinoid dysregulation in obesity: relation to intestinal motility and energy processing induced by food deprivation and re-feeding

Background and purpose:

Endocannabinoids in tissues controlling energy homeostasis are altered in obesity, thus contributing to metabolic disorders. Here we evaluate endocannabinoid dysregulation in the small intestine of mice with diet-induced obesity (DIO) and in peripheral tissues of Zucker and lean rats following food deprivation and re-feeding.

Experimental approach:

Intestinal transit, evaluated using rhodamine-B-labelled dextran, and small intestinal endocannabinoid levels, measured by liquid chromatography mass spectrometry, were measured in mice fed normal or high-fat diets (HFDs). Endocannabinoid levels were measured also in various tissues of lean and Zucker rats fed ad libitum or following overnight food deprivation with and without subsequent re-feeding.

Key results:

After 8 weeks of HFD, baseline intestinal transit was increased in DIO mice and enhanced by cannabinoid CB₁ receptor antagonism less efficaciously than in lean mice. Small intestinal anandamide and 2-arachidonoylglycerol levels were reduced and increased respectively. In Zucker rats, endocannabinoids levels were higher in the pancreas, liver and duodenum, and lower in the subcutaneous adipose tissue. Food deprivation increased endocannabinoid levels in the duodenum and liver of both rat strains, in the pancreas of lean rats and in adipose tissues of Zucker rats.

Conclusions and implications:

Reduced anandamide levels might account for increased intestinal motility in DIO mice. Regulation of endocannabinoid levels in rat peripheral tissues, induced by food deprivation and re-feeding, might participate in food intake and energy processing and was altered in Zucker rats. These data, together with previous observations, provide further evidence for dysregulation of peripheral endocannabinoids in obesity.     

Effects of age on hypertensive status in patients with chronic kidney disease

OBJECTIVE: To evaluate effect of age on hypertensive status in chronic kidney disease (CKD). METHODS: We studied 459 prevalent CKD patients (stages 2-5, no dialysis), grouped by age (< 55, 55-64, 65-74, >or= 75 years), undergoing clinical blood pressure (CBP) and ambulatory blood pressure (ABP) measurement. RESULTS: Prevalence of diabetes, left ventricular hypertrophy and previous cardiovascular disease progressively increased with aging; glomerular filtration rate (GFR) and hemoglobin decreased. Achievement of CBP target decreased from 16% in patients < 55 years to 6% in those >or= 75 years (P = 0.023). ABP 24-h systolic rose while diastolic decreased, with a consequent pulse pressure increase from 45 +/- 8 to 65 +/- 14 mmHg (P < 0.0001). Age, proteinuria, diabetes, cardiovascular disease and anemia but not GFR predicted higher 24-h pulse pressure. CBP overestimated systolic/diastolic daytime ABP by 14 +/- 18/7 +/- 11 mmHg on average, a greater difference in older than younger groups (P < 0.005). Conversely, CBP night-time ABP difference did not vary among groups (24 +/- 20/16 +/- 11 mmHg). These age-dependent differences determined a rising prevalence of white-coat hypertension (from 19 to 40%, P = 0.001) and night/day ratio of at least 0.9 (from 43 to 66%, P = 0.0004). Age, diabetes, left ventricular hypertrophy and anemia but not GFR predicted nondipping status. Among the oldest patients, 13% had diastolic CBP below 70 mmHg, with 48% below the corresponding values of daytime (< 69 mmHg) or night-time ABP (< 60 mmHg). CONCLUSION: In CKD, prevalence of white-coat hypertension, nondipping status and potentially dangerous low diastolic ABP increases with aging. This suggests wider use of ABP monitoring in older patients and need for trials addressing identification of an age-specific blood pressure target.     

Operative management of periprosthetic femur fractures in the elderly using biological fracture reduction and fixation techniques

Treatment of periprosthetic femur fractures often requires deviation from standard fixation techniques due to the presence of associated arthroplasty components, however, the use of adjuvant bone grafts and bone graft substitutes remain controversial. 59 patients (average age, 74 years) with either a periprosthetic femoral shaft about an arthroplasty stem (n=29) or supracondylar fracture above a total knee arthroplasty (n=30) were treated with biological open-reduction internal-fixation techniques without the use of bone grafts or bone-graft substitutes. All except one patient healed after the index procedure. Three patients had progressive malalignment associated with failed screw fixation but all healed without further surgical intervention. 49 out of the 59 patients returned to their baseline level of function. These results indicate that use of adjuvant bone graft materials may not be routinely necessary when treating periprosthetic femur fractures using lateral plates and biological reduction and fixation techniques.