Clinical and diagnostic findings in COVID-19 patients: an original research from SG Moscati Hospital in Taranto Italy.

The coronavirus disease 2019 (COVID-19) pandemic is a worldwide medical challenge due to the scarcity of proper information and remedial resources. The ability to efficiently avoid a further SARS-CoV-2 pandemic will, therefore, depend on understanding several factors which include host immunity, virus behavior, prevention measures, and new therapies. This is a multi-phase observatory study conducted in the SG Moscati Hospital of Taranto in Italy that was converted into COVID-19 Special Care Unit for SARS-Co-V2 risk management. Patients were admitted to the 118 Emergency Pre-Hospital and Emergency Department based on two diagnostic criteria, the nasopharyngeal swab assessed by reverse-transcriptase-polymerase-chain-reaction (RT-PCR) and CT-scan image characterized by ground glass opacity. Patients were divided into four groups, positive-positive (ER-PP), negative-positive (ER-NP), negative-negative (ER-NN) and a group admitted to the ICU (ER-IC). A further control group was added when the T and B lymphocyte subsets were analyzed. Data included gender, age, vital signs, arterial blood gas analysis (ABG), extensive laboratory results with microbiology and bronchoalveolar lavage fluid (BALF) which were analyzed and compared. Fundamental differences were reported among the groups. Males were significantly higher in PP, ICU, and NP groups, from 2 to 4-fold higher than females, while in the NN group, the number of females was mildly higher than males; the PP patients showed a marked alkalotic, hypoxic, hypocapnia ABG profile with hyperventilation at the time of admission; finally, the laboratory and microbiology results showed lymphopenia, fibrinogen, ESR, CRP, and eGFR were markedly anomalous. The total number of CD4+ and CD8+ T cells was dramatically reduced in COVID-19 patients with levels lower than the normal range delimited by 400/µL and 800/µL, respectively, and were negatively correlated with blood inflammatory responses.

Neuroprotective agents in the management of glaucoma.

Glaucoma is an optic neuropathy, specifically a neurodegenerative disease characterized by loss of retinal ganglion cells (RGCs) and their axons. The pathogenesis of RGC loss in glaucoma remains incompletely understood and a broad range of possible mechanisms have been implicated. Clinical evidence indicates that lowering intraocular pressure (IOP) does not prevent progression in all patients; therefore, risk factors other than those related to IOP are involved in the disease. The need for alternative, non-IOP-lowering treatments focused at preventing progression, that is, neuroprotectants, has become of interest to both the patient and the physician. Experimental evidence accumulated during the past two decades lend a great deal of support to molecules endowed with neuroprotective features. However, translation to the clinic of the latter drugs results unsuccessful mostly because of the lack of reliable in vivo measure of retinal damage, thus hampering the good therapeutic potential of neuroprotective agents given alone or as adjuvant therapy to IOP-lowering agents. Further research effort is needed to better understand the mechanisms involved in glaucoma and the means to translate into clinic neuroprotective drugs.

Rational Basis for the Use of Bergamot Essential Oil in Complementary Medicine to Treat Chronic Pain.

In complementary medicine, aromatherapy uses essential oils to improve agitation and aggression observed in dementia, mood, depression, anxiety and chronic pain. Preclinical research studies have reported that the essential oil obtained from bergamot (BEO) fruit (Citrus bergamia, Risso) modifies normal and pathological synaptic plasticity implicated, for instance, in nociceptive and neuropathic pain. Interestingly, recent results indicated that BEO modulates sensitive perception of pain in different models of nociceptive, inflammatory and neuropathic pain modulating endogenous systems. Thus, local administration of BEO inhibited the nociceptive behavioral effect induced by intraplantar injection of capsaicin or formalin in mice. Similar effects were observed with linalool and linalyl acetate, major volatile components of the phytocomplex, Pharmacological studies showed that the latter effects are reversed by local or systemic pretreatment with the opioid antagonist naloxone hydrochloride alike with naloxone methiodide, high affinity peripheral µ-opioid receptor antagonist. These results and the synergistic effect observed following systemic or intrathecal injection of an inactive dose of morphine with BEO or linalool indicated an activation of peripheral opioid system. Recently, in neuropathic pain models systemic or local administration of BEO or linalool induced antiallodynic effects. In particular, in partial sciatic nerve ligation (PSNL) model, intraplantar injection of the phytocomplex or linalool in the ipsilateral hindpaw, but not in the contralateral, reduced PSNL-induced extracellularsignal- regulated kinase (ERK) activation and mechanical allodynia. In neuropathic pain high doses of morphine are needed to reduce pain. Interestingly, combination of inactive doses of BEO or linalool with a low dose of morphine induced antiallodynic effects in mice. Peripheral cannabinoid and opioid systems appear to be involved in the antinociception produced by intraplantar injection of ß -caryophyllene, present in different essential oils including BEO. The data gathered so far indicate that the essential oil of bergamot is endowed with antinociceptive and antiallodynic effects and contribute to form the rational basis for rigorous testing of its efficacy in complementary medicine.

Coronary artery calcification and outcomes in diabetic patients with and without chronic kidney disease.

BACKGROUND/AIMS: Presence and progression of coronary artery calcification (CAC) indicate severe atherosclerosis and predict cardiovascular events (CVE) in dialysis (ESRD patients) and nondialysis patients (CKD patients). This study aimed at evaluating the prevalence and progression of CAC and CVE in CKD patients with diabetes in whom atherosclerosis of coronary arteries is the leading cause of CVE. METHODS: This was a retrospective study conducted in both out- and in-patients with chronic kidney disease, stage 2-5. CAC were assessed by the total calcium (TC) score. CT scans were performed at the entry and at the end of the study. RESULTS: Patients (n = 341) were divided into nondiabetic (n = 281) and diabetic patients (n = 60). CAC prevalence and TC score were higher in diabetics and associated with age, diabetes mellitus and pulse pressure. Diabetics with CKD presented a higher percentage of CAC progression and CVE. CONCLUSION: Prevalence, extent, progression of CAC and CVE are higher in diabetics with concomitant CKD. These findings may promote a more aggressive protocol of screening and care in type 2 diabetics with concomitant CKD.

An ethanol-based fixation method for anatomical and micro-morphological characterization of leaves of various tree species.

The use of formalin constitutes serious health hazards for laboratory workers. We investigated the suitability and performance of the ethanol-based fixative, FineFIX, as a substitute for formalin for anatomical and cellular structure investigations of leaves by light microscopy and for leaf surface and ultrastructural analysis by scanning electron microscopy (SEM). We compared the anatomical features of leaf materials prepared using conventional formalin fixation with the FineFIX. Leaves were collected from ornamental tree species commonly used in urban areas. FineFIX was also compared with glutaraldehyde fixation and air drying normally used for scanning electron microscopy to develop a new method for evaluating leaf morphology and microstructure in three ornamental tree species. The cytological features of the samples processed for histological analysis were well preserved by both fixatives as demonstrated by the absence of nuclear swelling or shrinkage, cell wall detachment or tissue flaking, and good presentation of cytoplasmic vacuolization. In addition, good preservation of surface details and the absence of shrinkage artefacts confirmed the efficacy of FineFIX fixation for SEM analysis. Cuticular wax was preserved only in air dried samples. Samples treated with chemical substances during the fixation and dehydration phases showed various alterations of the wax structures. In some air dried samples a loss of turgidity of the cells was observed that caused general wrinkling of the epidermal surfaces. Commercial FineFIX is an adequate substitute for formalin in histology and it can be applied successfully also for SEM investigation, while reducing the health risks of glutaraldehyde or other toxic fixatives. To investigate the potential for plants to absorb and capture particulates in air, which requires preservation of the natural morphology of trichomes and epicuticular waxes, a combination of FineFIX fixation and air drying is recommended.

Impact of ergonomics risk among workers in clothes central distribution service in a hospital.

BACKGROUND: In health care services, the workers from laundry and linen services are exposed to various occupational hazards, including the ergonomic risk. Were decided to study the effect of ergonomic factors at work in the musculoskeletal system for employees in this sector. METHODS: Cross-sectional study conducted in a mid-sized general hospital in Brazil. Site visit was conducted to apply recognition of occupational hazards and work activities flow. Medical evaluation of twenty-one workers was performed for designing the health status of them, focusing on orthopedic disorders. RESULTS: Their activities are to distribute clothes in all units of hospital care in order to organize and maintain supplies. The principal complaints were back pain (43%) and shoulder pain (24%). The ergonomic risk happens due to repeated movements of lumbar flexion in sealing, raising the arms above shoulder level in storage and transportation of loads on the distribution of clean clothes. CONCLUSIONS: The complaints by workers are consistent with the overloads identified in the evaluation of jobs. It is recommended to adjust anthropometrically the sealing workplace; the availability of stairs; the implantation of trolleys with four swivel wheels; short breaks during the workday; and to stretch the muscles before and during work.

Musculoskeletal disorder related to the work of doctors who perform medical invasive evaluation.

BACKGROUND: Experts in medical invasive evaluations, like colonoscopy, could be exposed to ergonomic risks during their work. Little attention has been given to these spectrum of occupational health. Its aimed to analyze possible clinical problems related to upper limb of physicians who perform those exams. METHODS: Cross-sectional study in a health service in Sao Paulo, Brazil. For evaluation of the workplace of the colonoscopist physician were applied two tools: Couto's check list and Sue Rodgers Method. The results direct the potential risk to upper limb injuries. RESULTS: The procedure is done and the final report is issued. There are no mandatory pauses during workday. The dominant hand holds the tube insertion with pincer movement during the exam, digital prehension being necessary at times. For this activity the employee has to use some strength. Couto's check list indicates a significant biomechanical factor. Sue Rodgers's Method states high ergonomic risk for dominant hand/wrist/fingers. CONCLUSION: The main risk for the development of health disorders are associated with the use of force and repetitive movements of hands. The adoption of regular breaks to recover most of the structures required is recommended.

Evaluation of lumbar overload in hotel maids.

BACKGROUND: Work-related musculoskeletal disorders are responsible for important amount of declining productivity among workers. Its economic impact is considered important because, in some aspects, such as sickness absence, it can cause increase in costs for employers. This paper aimed at identifying whether the activities that the hotel maids perform during working hours may lead to the development of musculoskeletal disorders. METHODS: Cross-sectional study conducted in a hotel in the city of São Paulo, Brazil. Performed an ergonomic analysis of the job application with a checklist consisting of risk assessment of low back pain. RESULTS: The maids are responsible for the cleaning of hotel rooms, including to lean in order to clean the bathroom. The activity is associated with ergonomic risk for poor posture, manual transport of loads and use of physical force in the upper limbs. This job presents a moderate risk of low back pain according to checklist for assessing the ergonomic situation. CONCLUSIONS: Negative ergonomic aspects are associated with the development or aggravation of musculoskeletal disorders in these workers. We suggest modification in work organisation. Another possibility is decreased the weight of the carts, keeping areas of replacement material on each floor.

Neuroprotection by leptin in a rat model of permanent cerebral ischemia: effects on STAT3 phosphorylation in discrete cells of the brain.

In addition to its effects in the hypothalamus to control body weight, leptin is involved in the regulation of neuronal function, development and survival. Recent findings have highlighted the neuroprotective effects of leptin against ischemic brain injury; however, to date, little is known about the role performed by the signal transducer and activator of transcription (STAT)-3, a major mediator of leptin receptor transduction pathway in the brain, in the beneficial effects of the hormone. Our data demonstrate that systemic acute administration of leptin produces neuroprotection in rats subjected to permanent middle cerebral artery occlusion (MCAo), as revealed by a significant reduction of the brain infarct volume and neurological deficit up to 7 days after the induction of ischemia. By combining a subcellular fractionation approach with immunohistofluorescence, we observe that neuroprotection is associated with a cell type-specific modulation of STAT3 phosphorylation in the ischemic cortex. The early enhancement of nuclear phospho-STAT3 induced by leptin in the astrocytes of the ischemic penumbra may contribute to a beneficial effect of these cells on the evolution of tissue damage. In addition, the elevation of phospho-STAT3 induced by leptin in the neurons after 24 h MCAo is associated with an increased expression of tissue inhibitor of matrix metalloproteinases-1 in the cortex, suggesting its possible involvement to the neuroprotection produced by the adipokine.

Calpain-mediated cleavage of Beclin-1 and autophagy deregulation following retinal ischemic injury in vivo.

Autophagy is the major intracellular degradation pathway that regulates long-lived proteins and organelles turnover. This process occurs at basal levels in all cells but it is rapidly upregulated in response to starvation and cellular stress. Although being recently implicated in neurodegeneration, it remains still unclear whether autophagy has a detrimental or protective role. In this study, we investigated the dynamics of the autophagic process in retinal tissue that has undergone transient ischemia, an experimental model that recapitulates features of ocular pathologies, including glaucoma, anterior ischemic optic neuropathy and retinal vessels occlusion. Retinal ischemia, induced in adult rats by increasing the intraocular pressure, was characterized by a reduction in the phosphatidylethanolamine-modified form of LC3 (LC3II) and by a significant decrease in Beclin-1. The latter event was associated with a proteolytic cleavage of Beclin-1, leading to the accumulation of a 50-kDa fragment. This event was prevented by intravitreal treatment with the non-competitive N-methyl-D-aspartate antagonist MK801 and calpain inhibitors or by calpain knockdown. Blockade of autophagy by pharmacological inhibition or Beclin-1 silencing in RGC-5 increased cell death, suggesting a pro-survival role of the autophagic process in this neuronal cell type. Altogether, our results provide original evidence for calpain-mediated cleavage of Beclin-1 and deregulation of basal autophagy in the rat retina that has undergone ocular ischemia/reperfusion injury.

Modulation of pro-survival and death-associated pathways under retinal ischemia/reperfusion: effects of NMDA receptor blockade.

Loss of retinal ganglion cells occurs in a variety of pathological conditions, including central retinal artery occlusion, diabetes and glaucoma. Using an experimental model of retinal ischemia induced by transiently raise the intraocular pressure (IOP), In this study, we report the original observation that ischemic retinal ganglion cells death is associated with the transient deactivation of the pro-survival kinase Akt and activation of GSK-3beta followed, during reperfusion, by a longer lasting, PI3K-dependent, activation of Akt and phosphorylation of GSK-3beta. Under these experimental conditions, retinal ischemia induced the expression of Bad, a pro-apoptotic protein, member of the Bcl-2 family. The detrimental effects yielded by the ischemic stimulus were minimized by intravitreal administration of the NMDA receptor antagonist, MK801, that reduced the expression of Bad and significantly increased Akt phosphorylation. In conclusion, our present results contribute to unravel the mechanisms underlying retinal damage by high IOP-induced transient ischemia in rat. In addition, these data implicate the pro-survival PI3K/Akt pathway and the observed reduced expression of Bad in the neuroprotection afforded by MK801.

Cell signaling pathways in the mechanisms of neuroprotection afforded by bergamot essential oil against NMDA-induced cell death in vitro.

BACKGROUND AND PURPOSE: The effects of bergamot essential oil (BEO; Citrus bergamia, Risso) on excitotoxic neuronal damage was investigated in vitro. EXPERIMENTAL APPROACH: The study was performed in human SH-SY5Y neuroblastoma cells exposed to N-methyl-D-aspartate (NMDA). Cell viability was measured by dye exclusion. Reactive oxygen species (ROS) and caspase-3 activity were measured fluorimetrically. Calpain I activity and the activation (phosphorylation) of Akt and glycogen synthase kinase-3beta (GSK-3beta) were assayed by Western blotting. KEY RESULTS: NMDA induced concentration-dependent, receptor-mediated, death of SH-SY5Y cells, ranging from 11 to 25% (0.25-5 mM). Cell death induced by 1 mM NMDA (21%) was preceded by a significant accumulation of intracellular ROS and by a rapid activation of the calcium-activated protease calpain I. In addition, NMDA caused a rapid deactivation of Akt kinase and this preceded the detrimental activation of the downstream kinase, GSK-3beta. BEO (0.0005-0.01%) concentration dependently reduced death of SH-SY5Y cells caused by 1 mM NMDA. In addition to preventing ROS accumulation and activation of calpain, BEO (0.01%) counteracted the deactivation of Akt and the consequent activation of GSK-3beta, induced by NMDA. Results obtained by using specific fractions of BEO, suggested that monoterpene hydrocarbons were responsible for neuroprotection afforded by BEO against NMDA-induced cell death. CONCLUSIONS AND IMPLICATIONS: Our data demonstrate that BEO reduces neuronal damage caused in vitro by excitotoxic stimuli and that this neuroprotection was associated with prevention of injury-induced engagement of critical death pathways.

Outcomes of a pharmacoepidemiological survey on the antibiotic treatment of uncomplicated acute cystitis in community.

We carried out a community-based survey in order to emphasize the importance of therapeutic appropriateness of antibiotic prescription by local physicians and the close connection between pharmacotherapy and pharmacoeconomics. Twenty general practitioners belonging to the local sanitary firm of Paola (CS, Italy) provided information, including their prescription, regarding 64 patients, both male and female, presenting clinical symptoms of uncomplicated acute cystitis. The data collected were compared with those of a previous trial performed in the same setting and documenting the effectiveness and advantages associated with the use of amoxicillin against community-acquired uncomplicated urinary tract infections (UTI). By comparing the prescriptive behaviour of physicians between the first and the present survey, we detected a significant increase in the use of amoxicillin (from 0 to 26.56%), paralleled by a decrease in prescribing aminoglycosides (from 18.18 to 1.56%). In addition, this resulted in a significant reduction in the costs of treatment (from 23.06 to 12.75 euros). Therefore, given the vast consensus concerning the adoption of empirical treatment for the eradication of UTI, the present survey underlines the crucial role of local antibiotic resistance monitoring in order to optimize the use of these drugs. Moreover, we have also observed a significant reduction in treatment costs associated with an appropriate and effective treatment of UTI.

Rational use of antibiotics in acute uncomplicated cystitis: a pharmaco-epidemiological study.

Uncomplicated community-acquired urinary tract infections are among those most commonly found in clinical practice, resulting in significant morbidity and health care costs. Current management is usually empirical because of the narrow and predictable spectrum of etiologic agents that cause acute cystitis and their susceptibility patterns. However, since antimicrobial resistance is increasing, the use narrow-spectrum, inexpensive antimicrobial agents becomes less feasible. In our study we have evaluated the effectiveness of amoxicillin, a narrow-spectrum, inexpensive and non toxic drug, against non-complicated acute cystitis in 34 patients, and compared the results with the antibiotic therapy previously employed by the physicians of the Health Care Unit of Paola (CS), Italy. Amoxicillin was found to be effective for the treatment of community-acquired cystitis, thus suggesting that the development of bacterial resistance does not represent a limit to its use. Furthermore, our study demonstrates that besides providing an effective alternative to broad-spectrum antibiotics, the use of amoxicillin significantly reduced health care costs.

A simple method for correcting overestimated glomerular filtration rate in obese subjects evaluated by the Cockcroft and Gault formula: a comparison with 51Cr EDTA clearance.

AIM: The Cockcroft and Gault formula is a quick and reliable method for calculating creatinine clearance without a 24-hour urine collection (CG-cl). In obese subjects an excess of fat mass provokes a reduction in daily creatinine urine excretion per body kilo weight and is responsible for overestimated renal function when calculated by CG-cl. The aim of this study was to devise a simple correction method which could also make use of CG-cl in obese subjects. PATIENTS AND METHODS: In 52 subjects with a body mass index (BMI) > 25, renal function was assessed by simultaneously determining creatinine clearance using 24-hour urine collection (Cr-cl) and the CG-cl. The percentage difference between the 2 clearances (delta %) was correlated with BMI for each patient using simple linear regression analysis. The estimated regression model (delta% = 1.217 BMI-- 24.81) provided the following CG-cl correction formula for obese subjects: Corrected CG-cl = CG-cl (1.25 - 0.012 BMI). Its validity was evaluated in another group of 20 subjects with BMI > 25 by comparing the results obtained with Corrected CG-cl to those obtained by CG-cl and MDRD formula (MDRD-cl) using the clearance of 51Cr-EDTA (5 Cr-EDTA-cl) as the GFR measurement gold standard. RESULTS AND CONCLUSION: Linear regression analysis of CG-cl, MDRD-cl and Corrected CG-cl compared to 5tCr-EDTA-cl (considered as the independent variable) resulted in the following determination coefficients (R2): 0.687; 0.818; 0.947, respectively. In conclusion, this formula can be considered a quick and reliable method for CG-cl correction in obese subjects.

Inducible nitric oxide synthase is involved in the mechanisms of cocaine enhanced neuronal apoptosis induced by HIV-1 gp120 in the neocortex of rat.

Cocaine, often abused by human immunodeficiency virus (HIV) infected patients, has been suggested to worsen the HIV associated dementia via unknown mechanisms. Here we report that subchronic treatment with a dose of cocaine (30 mg/kg i.p.), unable per se to cause neuronal death, increases the number of apoptotic cells typically observed in the neocortex of rats treated with HIV-1 gp120 (100 ng given i.c.v.). A pre-treatment with MK801 (0.3 mg/kg i.p.), a NMDA receptor antagonist, L-NAME (10 mg/kg i.p.) and 7-nitroindazole (50 mg/kg i.p.), two specific inhibitors of NOS, or with 1400 W (1 mg/kg s.c.), a selective inhibitor of inducible NOS (iNOS), minimized neurotoxicity by combined administration of cocaine and gp120 thus implicating iNOS. This conclusion is supported by the evidence that cocaine increases brain neocortical citrulline, the co-product of NO synthesis.

A rare case of central post-gravid diabetes insipidus.

Central diabetes insipidus (CDI) arising in the puerperal period has been attributed mainly to Sheehan's syndrome or to lymphocytic infundibulo-neurohypophysitis. We report the case of a 24-year-old woman who came to our observation for the appearance, 3 weeks after a normal delivery, of a polyuric-polydipsic syndrome. Measurements of urinary volumes, plasma osmolality and urinary osmolality, in conditions of free water intake, water deprivation and a water deprivation-vasopressin administration test, demonstrated CDI. Brain magnetic resonance imaging showed a normal morphology of the adenohypophysis and total absence of the neurohypophysis. Assays of the pituitary hormones were found to be within normal limits. These results, incompatible with a diagnosis of Sheehan's syndrome and lymphocytic infundibulo-neurohypophysis, excluded all the other known causes of acquired CDI. Our diagnosis was therefore of post-gravid idiopathic CDI. Thus, it is possible that in the puerperal period other diseases of the posterior hypophysis may develop, of unknown etiopathogenesis but equally responsible for CDI.

Nitrendipine and amlodipine mimic the acute effects of enalapril on renal haemodynamics and reduce glomerular hyperfiltration in patients with chronic kidney disease.

Antihypertensive drugs may have an important effect on glomerular haemodynamics. In chronic nephropathy patients, we compared the effect on glomerular haemodynamics of two second-generation dihydropyridinic agents, nitrendipine and amlodipine, with a first generation dihydropyridinic agent and an ACE-inhibitor, enalapril. In all, 32 patients (pts), divided into four groups, received the different drugs: ENA (enalapril, eight pts), NIF (nifedipine, eight pts), NIT (nitrendipine, eight pts) AML (amlodipine, eight pts). The study assessed the effect on glomerular haemodynamics of a single administration of the test drug in baseline conditions and in glomerular hyperfiltration experimentally induced by amino-acid infusion. The glomerular filtration rate (GFR, measured by inulin clearance), effective renal plasma flow (ERPF, measured by p-aminohippurate clearance), renal vascular resistances (RVR) and filtration fraction (FF) were assessed. Administration of AML and NIT test dose reduced FF, as did ENA, but not NIF, in both baseline (AML: P=0.005; NIT: P=0.02; ENA: P=0.007) and glomerular hyperfiltration conditions (AML: P=0.0003; NIT: P=0.03; ENA: P=0.00006). In baseline conditions, only ENA resulted in a significant drop in the GFR (P=0.008), while NIF, NIT and AML induced a significant increase (P=0.003, 0.03, 0.0001, respectively). However, in hyperfiltration conditions, NIT (0.08) and AML (0.00003) caused a decrease in the GFR, as did ENA (0.0003) but not NIF. In all the experimental conditions, a RVR reduction and an ERPF increase were observed. Single dose of NIT and AML were effective in attenuating the effect of amino-acid infusion on glomerular filtration, similar to ENA; this effect of NIT and AML on the glomerular filtration rate is not observed under basal conditions.

Apoptosis in the mechanisms of neuronal plasticity in the developing visual system.

Visual experience during early postnatal life is essential for normal development of synaptic connections in the visual system. In fact, altered visual experiences such as monocular deprivation (MD) or abnormal visual stimulation (e.g. strabismus, anisometropia) during this period disrupt the physiologic organization of the visual pathway, leading to loss of visual responses in cortical neurons and reduction in visual acuity of the affected eye, so that it becomes amblyopic. The authors review the main functional and morphologic changes induced by altered visual experiences in the developing visual system and focus on the recent discovery that MD induces apoptotic cell death in the lateral geniculate nucleus of newborn rats. Particular attention is given to the authors' studies documenting that, during development, MD leads retinal terminals to release excessive glutamate in the lateral geniculate nucleus where it elevates nitric oxide and causes DNA fragmentation. The latter event is known to activate poly-(ADP-ribose) polymerase, which in turn may trigger apoptosis. Better understanding of the mechanisms underlying the morphologic changes induced by altered visual experiences during development may open new venues for studying novel neuroprotective strategies for amblyopia and, more generally, for the treatment of ophthalmic diseases associated with neuronal apoptosis.

Effectiveness of long-term heparin-induced extracorporeal LDL precipitation (HELP) in improving coronary calcifications.

There is clear clinical evidence that a drastic lowering of plasma LDL-Cholesterol (LDL) concentrations significantly reduces the rate of total and coronary mortality as well as the incidence of cardiovascular events in high risk hypercholesterolemic patients. We describe the case of a 51-year-old woman with coronary heart disease (CHD) who presented with increasing angina on exertion in 1995, at the age of 45. She suffered from a heterozygous familial hypercholesterolemia and in 1985 her total cholesterol (TCHO) was 328 +/- 62 mg/dl (mean value of ten analysis). After ten years of statins her mean values (20 analysis, 2 per year) were: TCHO 259 +/- 71, LDL 209 +/- 47, HDL 35 +/- 7 mg/dl. Coronary angiography (CA) performed in 1995 disclosed three vessel coronary heart disease with significant stenoses of the distal right coronary artery, multiple calcifications of the interventricularis artery and multiple plaques with significant stenoses in the ramus circumflexus. The woman underwent coronary by-pass surgery. Thereafter the patient was treated for six years with HELP in biweekly intervals, in combination with statins. TCHO, LDL, HDL and fibrinogen (fb) levels were measured before and after each treatment. Their mean values for an amount of 120 sessions were: TCHO pre 216 +/- 23, post 111 +/- 18 LDL pre 152 +/- 16 post 67 +/- 18, HDL pre 42 +/- 5 post 35 +/- 4 fb pre 306 +/- 48 post 125 +/- 31. In 2001 a new CA was performed. Calcifications disappeared and stenoses were identical to the previous CA or reduced. There were no further clinical manifestations of CHD. We trust that the clinical benefit of the HELP procedure will be substantial for those patients who have problems in clearing LDL from their plasma pool and who are at the same time sensitive to elevated LDL levels by the development of premature coronary sclerosis.