Lens protein glycation and the subsequent degree of opacity in streptozotocin-diabetic rats

We measured how much glycated protein there was in rat eye lenses with different degrees of cataract, using an antibody against glucitol-lysine. Streptozotocin-diabetic (STZ) rats were in some cases treated with insulin (STZ + INS); control rats were normal. We graded the cataracts from 0 (transparent) to 3 (entirely opaque). STZ rats had significantly more grade 3 cataracts, and STZ + INS rats more grade 1 cataracts, than other groups. Grade 3 lenses had significantly more glycated protein than those of grade 0 (10.8 +/- 2.7 vs. 1.0 +/- 0.4 nmol/mg protein), grades 1 and 2 being intermediate. Glycosylated hemoglobin levels correlated similarly with severity of cataract. These data are consistent with the greater incidence of cataract among diabetics than among non-diabetics, and suggest that lens protein glycation contributes to the development of cataract.     

Does milk have a cataractogenic effect?

We undertook a prospective study to test Simoons' hypothesis that in certain susceptible races milk exerts a cataractogenic effect. Overall milk intake in low lactase deficiency areas did not correlate with cataract occurrence. Subgrouping of cataract patients revealed that greater milk intake did show positive correlation with cortical cataracts. Cortical cataracts were also markedly more common in females. Analysis of data from three different regions showed greater milk intake in cortical cataract patients only. Our data indicate the importance of specifying cataract type in cataract studies and highlight the problem this approach brings forth. We noted no different trends in subjects from northwest and southeast India, although the number of subjects from the southeast was considerably less. Patients with early cortical cataracts may be advised to restrict milk intake.Part of this material was presented at second cataract epidemiology meeting at Bonn in March 1988. A brief report has been accepted for publication in the proceedings of the meeting to be published inDevelopment of Ophthalmology, Vol. 17, 1988.     

Diabetic cataracts: mechanisms and management

Diabetes mellitus is associated with a 5‐fold higher prevalence of cataracts, which remains a major cause of blindness in the world. Typical diabetic cataracts contain cortical and/or posterior subcapsular opacities. Adult onset diabetic cataracts also often contain nuclear opacities. Mechanisms of diabetic cataractogenesis have been studied in less detail than those of other diabetic complications. Both animal and human studies support important contribution of increased aldose reductase activity. Surgical extraction is the only cure of diabetic cataract today. An improved understanding of pathogenetic mechanisms, together with finding effective therapeutic agents, remain highest priority for diabetic cataract‐related research and pharmaceutical development. Copyright © 2010 John Wiley & Sons, Ltd.     

Gender effect on onset,prevalence and surgical treatment of cataract in patients with Myotonic Dystrophy type 1

Myotonic Dystrophy type 1 (DM1) is the most common muscular dystrophy in adults, affecting 1:8000 individuals. It is a multi-systemic disorder involving muscle, heart, endocrine and respiratory apparatus and eye. The eye symptoms can include ptosis, external ophthalmoplegia, epiphora, and early onset cataracts. Cataracts occur at a much earlier age (usually between 30 and 40) than the general population, where females are usually affected more than men. We studied gender differences in cataract prevalence and treatment age in 243 DM1 patients (134 M; 109 F), aged 18 to 70 years, who were subsequently screened at routine follow-up. For each patient, information was collected on age, sex, CTG expansion, age of cataract onset, and age at cataract surgery, when available.Seventy-three patients, 30 females and 43 males, had cataracts, at a mean age of onset of 41.14 ± 12.64 in females, and 40.36 ± 10.03 in males. Sixty-nine of them underwent cataract surgery, males at an earlier age than females (42.8 ± 9.8 years versus 47.3 ± 12.6 years) and in 52.5% of cases before the age of 40, compared to 17.2% of females. The difference was statistically significant. The assumption that females in general and those with DM1 in particular develop cataracts more frequently and earlier than males is not confirmed, at least in this study. A possible explanation for these results could be related to non-advanced age, the protective role of estrogen and the lower prevalence of smoking in the study population.Key words: Myotonic Dystrophy type 1, Steinert disease, gender, cataract, cataract surgery, prevalence     

Ocular associations of metabolic syndrome

Metabolic syndrome is a cluster of diseases including central obesity, dyslipidemia, hyperglycemia, and high blood pressure. People with metabolic syndrome have been shown to be at an increased risk of developing cardiovascular disease, beyond the risk associated with individual components of the syndrome. The association of diabetes and hypertension with retinopathy, cataract, and raised intraocular pressure is well known. This review highlights the association of metabolic syndrome, including all its components, with various ocular conditions such as retinopathy, central retinal artery occlusion, cataracts, and raised intraocular pressure.     

The Nutritional Teamwork Approach: Prevention and Regression of Cataracts in Rats

WE HAVE TAKEN ADVANTAGE OF A NEWLY ASSIMILATED PRINCIPLE IN NUTRITION: no nutrient by itself should be expected to prevent or cure any disease; nutrients as such always work cooperatively in metabolism as a team.By feeding galactose-containing diets to young rats, cataracts are regularly produced. When, however, we furnished galactose-fed animals with what may be considered a well balanced, full team of nutrients, cataract prevention was accomplished. On four galactose-containing diets supplied with a full team of nutrients, not a single cataract developed in 24 rats (48 eyes). On four diets using the same dietary galactose challenge, accompanied with inadequate nutritional teams, 47 out of 48 eyes developed cataracts. Diets of intermediate quality induced the development of intermediate numbers of cataracts. Cataracts once formed were regressed slowly and incompletely by shifting the animals to a diet similar to that which had previously been found to protect against cataract formation.The significance of these findings for nutritional research and for attacks on the problems of human cataracts and other ailments is discussed.     

The HOPE Asia Network activity for “zero” cardiovascular events in Asia: Overview 2020

The impact of hypertension‐related cardiovascular disease and target organ damage, and therefore the benefits of blood pressure (BP) control, is greater in Asian than in Western countries. Asia‐specific features of hypertension and its effective management are important and active areas of research. The Hypertension Cardiovascular Outcome Prevention and Evidence in Asia (HOPE Asia) Network was formed in 2016 and is now a member of the World Hypertension League. The main goal of the HOPE Asia Network is to improve the management of hypertension and organ protection toward achieving “zero” cardiovascular events in Asia. Considerable work has already been done on the journey to achieving this goal. We have shown that BP control status in Asia differs between countries, and even between regions within the same country. Several expert panel consensus recommendations and clinical guidance papers are available to support the use of home and ambulatory BP monitoring in the region. In addition, the AsiaBP@Home study prospectively investigated home BP control status across 15 specialist centers using the same validated device and measurement schedule. We have also proposed the concept of systemic hemodynamic atherothrombotic syndrome (SHATS), a vicious cycle of BP variability and vascular disease on cardiovascular events and organ damage, and suggested a SHATS score for risk stratification for clinical practice. This special issue of the journal collates Asia‐specific resources and data, contributing to advances in hypertension management and cardiovascular disease prevention in the region.     

Senile cataracts and oxidative stress

In numerous epidemiological and animal models, it can be inferred that oxidative stress is a key factor in cataract formation. Production of reactive oxygen species and reduction of endogenous antioxidants both contribute to cataract formation. In the cataractogenous process, lens proteins lose sulfhydryl groups and become thiolated or cross-linked by disulfide bonds. The resultant high molecular weight aggregates become insoluble and affect lens transparency. All these are consequences of changes in the redox state. A mixed protein-thiol and protein-protein disulfide bond precedes the morphological changes of cataract. Normally, sustained high levels of reduced glutathione provide a protective effect, while depletion of glutathione causes damage to epithelial cells and fiber cells. UV rays in the ambient environment evoke reactive oxygen species formation and also contribute to cataracts. The reduction in free UV filters and increase in their binding to lens proteins make the lens more predisposed to UV damage and oxidation. In the aqueous humor of cataract lenses, there is a decrease in antioxidant enzymes and increase in nitric oxide, which demonstrates the relationship between oxidative stress and cataracts. Though surgical intervention is the standard treatment for cataracts, experimental medical therapies for cataracts are under extensive investigation. Carnosine, a pro-drug of carnosine-N-acetylcarnosine, bendazac, ascorbic acid, and aldose reductase inhibitors are under therapeutic evaluation, and prevention of cataract formation may be possible in the future.     

Validity of the Distinction Between “Substance-Induced” and “Independent” Depression and Anxiety Disorders

Diagnosis of comorbid psychiatric disorders in substance abuse patients is complicated by the fact that many abused substances induce transient symptoms that mimic independent disorders. The authors applied criteria designed to distinguish “independent” comorbid disorders from those that may have been “substance-induced,” to determine the impact on rates of diagnosis and on concurrent and predictive validity. Of those with symptoms sufficient to meet criteria for comorbid depression (12%) or anxiety diagnoses (26%), fewer than one-fourth were considered to have independent disorders, and these patients did not constitute a category of greater severity. Current guidelines for defining independent diagnoses were not supported. Further work is required to identify criteria that will provide a clinically meaningful distinction.     

Senile cataract: a review on free radical related pathogenesis and antioxidant prevention

Glutathione metabolism plays an essential role in the homeostasis of the lens. Thus, it is not surprising that experimental depletion of this substance leads to a process of lens disorganization similar to senile cataract and that in all types of irreversible cataract there is a decrease in the glutathione content of the lens. Therefore, it may be useful in preventive geriatrics to raise the glutathione concentration of the lens and, since glutathione monoethyl ester can cross the capsule and membranes of the lens, administration of this compound may be the treatment of choice. This could be complemented by long-term administration of small doses of acetylsalicylic acid, in the early stages of the development of cataracts. The data also suggest that, in the 'high lactose absorbers', diets deprived of lactose (in addition to antioxidant administration) may play a role in protecting against cataract development and may even reverse some of the early changes that occur in cataractous lenses. The present review provides a justification for detection of cataract risk factors (high lactose absorption and low antioxidant protection in blood) as well as for preventive and palliative treatment of cataracts by administration of physiological antioxidants.     

Cataracts and hypertension in salt-sensitive rats. A possible ion transport defect

In previous unrelated studies, we observed a 35 to 50% incidence of cataract formation in several groups of Dahl salt-sensitive hypertensive rats (DS) over a 4-year period. In the present study we evaluated longitudinal changes in blood pressure in DS in which cataracts eventually developed and those in which cataracts did not develop when all animals were maintained on a high sodium diet. Lenses were evaluated by slit-lamp microscopy to determine if cataractous lesions were similar among rats, to classify lesion types, and to define the age at which cataracts were detectable in DS. The possible participation of several cataractogenic risk factors as major influences on cataract formation also was evaluated. Finally, aqueous humor concentrations and lenticular content of sodium and potassium were determined to evaluate the possibility that a defect in ion transport at the lens epithelium and ciliary body might play a role in cataractogenesis in DS, since ion transport defects have been shown to lead to lens opacification in other models of genetic and experimental cataracts. Parallel studies were performed in Dahl salt-resistant control rats (DR). A high incidence of cataract formation was found in DS. Although systolic blood pressure was not consistently greater in adult DS with cataracts compared with values in age-matched DS without cataracts, the initial pressor response to a high salt diet was greatest in weanling DS in which cataractous lesions later developed. Slit-lamp analysis revealed that cataracts in this genetic model were cortical, with one mixed cortical, nuclear lesion. Posterior subcapsular lesions were not observed, suggesting that lesions were not steroid-induced.(ABSTRACT TRUNCATED AT 250 WORDS)     

Progressive juvenile-onset punctate cataracts caused by mutation of the γD-crystallin gene

Cataracts are a significant public health problem. Here, we describe the genetic alteration responsible for a progressive form of cataract, segregating as an autosomal dominant trait in a three-generation pedigree. Unlike most autosomal dominant cataracts, these are not clinically apparent at birth but are initially observed in the first year or two of life. The opacification evolves relatively slowly, generally necessitating removal of the lens in childhood or early adolescence. A genome-wide search in our kindred revealed linkage at 2q33–35 where the γ-crystallin gene cluster resides. A single base alteration resulting in an Arg- 14→Cys (R14C) substitution in γD-crystallin was subsequently identified. Protein modeling suggests that the effect of this mutation is a subtle one, affecting the surface properties of the crystallin molecule rather than its tertiary structure, consistent with the fact that the patients’ lenses are normal at birth. This is the first gene defect shown to be responsible for a noncongenital progressive cataract, and studying the defective protein should teach us more about the mechanisms underlying cataract formation.     

Spontaneous resolution of a unilateral cataract in an adult: A case report

Rationale:Cataracts are a disease that is usually caused by aging and involve the irreversible degeneration of the lens material. On the other hand, transient cataracts have also been reported, mainly due to systemic hyperglycemia, which often occurs bilaterally. However, reports of the spontaneous regression of unilaterally occurring cataracts in patients with normal blood glucose levels are rare. Here, we report a rare case of spontaneous regression of unilateral posterior subcapsular cataracts in an adult with normal blood glucose levels.Patient concerns:A 42-year-old woman presented with distorted vision in her right eye. The patient was taking medication for diabetes, and her blood sugar level was well-controlled.Diagnosis:Upon examination, her uncorrected visual acuity and best-corrected visual acuity were 20/70 in her right eye. Slit lamp microscopy revealed fine, feathery, and streak-like posterior subcapsular opacities. Color fundus photography revealed a star-shaped shadow due to the cataract, and no diabetic retinopathy was observed. Her two hour postprandial glucose level was 115 mg/dL. The patient was diagnosed with posterior subcapsular cataracts, and cataract surgery was planned. The patient was scheduled to visit the clinic again after seven days.Interventions:Close observation for one week without any intervention.Outcomes:After one week, most of the posterior subcapsular opacities disappeared, and the uncorrected visual acuity and best-corrected visual acuity in the right eye improved to 20/40 and 20/30, respectively.Lessons:This case report demonstrates that unilateral posterior subcapsular cataracts may spontaneously regress in patients with normal blood glucose levels. Therefore, it is important to check whether cataracts improve spontaneously through short-term close follow-up before planning cataract surgery to avoid unnecessary surgery.     

Assessment of Efficacy and Safety of Combining “Paclitaxel” Eluting Balloon and “Limus” Eluting Stent in the Same Lesion

Objectives

To assess the safety and efficacy of combining drug‐eluting balloon (DEB) and drug‐eluting stents (DES) in the same coronary lesion.

Background

Use of DEB may not always produce optimal results or even result in dissection, compelling the operators to consider bailout stenting with bare metal stents (BMS). However, BMS may not be ideal in patients who have significant risk‐profile for restenosis. We have opted for DES over BMS in such situations and present our follow‐up data.

Methods

Between 2009 and 2011, 46 patients (57 lesions) requiring bailout stenting following DEB use were treated with second‐generation DES. All patients had at‐least one or more risk‐factors that made them vulnerable for restenosis (diabetes, chronic kidney disease, previous in‐stent restenosis [ISR], and/or long diffuse lesions ≥30 mm).

Results

Of the 57 lesions, 34 (60%) were previous ISR. The mean length of the DEB was: 36.2 ± 5.6 mm. All patients had TIMI‐3 flow post PCI with no in‐lab complications. At median follow‐up of 12.3 months (interquartile range [IQR]: 7.5–18.1), the rates target lesion revascularization (TLR) and target vessel revascularization (TVR) were 3 (5.3%) and 4 (7%), respectively. One patient had died 3 months following treatment. There were no episodes of myocardial infarction, definite or probable stent thrombosis. The major adverse cardiovascular events (MACE) rate defined as cardiac‐death, MI, and TVR occurred in 11% of patients.

Conclusion

The results from this novel strategy of combining “Paclitaxel” eluting balloon and “Limus” eluting stent in a same lesion are encouraging. Dual drug‐elution acting on two different pathways may provide potential synergy that may explain the favorable outcome. (J Interven Cardiol 2013;26:259–263)

     

Identification of “substrate fibrillators” and “trigger fibrillators” by pacemaker diagnostics

BACKGROUND: The population of patients likely to respond to selected pacing algorithms for maintenance of sinus rhythm is unknown. OBJECTIVES: The purpose of this study was to identify patients with specific onset patterns of paroxysmal atrial fibrillation (AF). METHODS: Dual-chamber pacemakers with advanced diagnostic functions were implanted in 112 patients with conventional indications for antibradycardia pacing and a history of paroxysmal AF. Pacemaker diagnostic data were analyzed after 97.5 +/- 40.9 days. According to the frequency of premature atrial contractions (PACs) during the 5 minutes before AF onset, patients were assigned to one of three groups: group A (high PAC activity), group B (moderate PAC activity), or group C (low PAC activity). RESULTS: AF burden was lower in group A (4.6% +/- 2.4%) than group B (15.8% +/- 3.0%, P = .003) and group C (15.5% +/- 3.1%, P = .003). Fewer AF episodes occurred in group A (2.1 +/- 1.3 per day) than group B (3.8 +/- 1.2 per day, P = .006). Mean AF episode duration was shorter in group A (11.4 +/- 10.2 hours) than group C (41.4 +/- 27.5 hours, P = .03). CONCLUSION: The coincidence of low PAC activity before AF onset, high AF burden, and extended arrhythmia episode duration appears to be the consequence of a high atrial substrate factor. In these "substrate fibrillators," the efficacy of pacing algorithms for maintenance of sinus rhythm may be limited. In contrast, "trigger fibrillators" exhibiting low AF burden despite high PAC incidence may represent the target population for specific PAC-suppressing pacing algorithms.     

Effect of exposure to hyperbaric oxygen on diabetes-induced cataracts in mice

Background: The growth‐associated increase in the blood glucose level of animals with Type 2 diabetes is inhibited by moderate hyperbaric exposure at 1.25 atmospheres absolute (ata) with 36% oxygen, presumably due to an increase in oxidative metabolism. However, there are no data available regarding the effect of moderate hyperbaric oxygen (HBO) on diabetes‐induced cataracts. Methods: Four‐week‐old mice with Type 2 diabetes and cataracts were exposed to 1.25 ata with 36% oxygen, 6 h daily, for 12 weeks, followed by normal conditions at 1 ata with 21% oxygen for 16 weeks (cataract + hyperbaric group). Levels of blood glucose and derivatives of reactive oxygen metabolites (dROMs), used as an index of oxidative stress, and the turbidities of the lenses from these mice at 4, 8, 12, 16, and 32 weeks of age were compared with those of control and diabetic (cataract group) mice not exposed to HBO. Results: Non‐fasting and fasting blood glucose levels were lower in the cataract + hyperbaric group at 12, 16, and 32 weeks of age than in the age‐matched cataract group. The levels of dROMs were lower in the cataract + hyperbaric group at 16 and 32 weeks of age than in the age‐matched cataract group. The turbidities of the peripheral and central regions of the lenses were lower in the cataract + hyperbaric group at 12, 16, and 32 weeks of age than in the age‐matched cataract group. Conclusions: Hyperbaric exposure at 1.25 ata with 36% oxygen delays cataract development and progression in mice with Type 2 diabetes.     

Cardiac resynchronization therapy: “Nonresponders” and “hyperresponders”

BACKGROUND: Cardiac resynchronization therapy (CRT) is a recognized treatment modality for patients with dilated cardiomyopathy (DCM), left bundle branch block, and severe cardiac failure. However, 30% of patients are "nonresponders." Intriguingly, the opposite case has not been reported until recently: Do some patients treated with CRT have a "complete" recovery and thus can be considered "hyperresponders"? OBJECTIVE: The purpose of this study was to investigate patients treated with CRT who have a "complete" functional recovery, with normalization of left ventricular function after therapy. METHODS: Eighty-four consecutive patients with DCM, sinus rhythm, and left bundle branch block in New York Heart Association functional class III and IV who were implanted with a CRT device were prospectively followed. Patients were considered to be "hyperresponders" if they concurrently fulfilled two criteria: functional recovery and left ventricular ejection fraction > or = 50%. RESULTS: Among the 84 patients with DCM, 11 (13%) were "hyperresponders" within 6 to 24 months after CRT (left ventricular ejection fraction increased from 25% +/- 8% to 60% +/- 6.5%, P = .001). Comparison of baseline parameters between "hyperresponders" and the remaining patients showed that only etiology of the DCM was statistically discriminative. All "hyperresponders" belonged to the group of patients with nonischemic DCM (18% vs 0%, P = .05). CONCLUSION: In a subset of patients successfully implanted with a CRT device, "complete" functional recovery associated with normalization of LV function was observed, giving rise to the concept of "hyperresponders." This finding is observed exclusively in the subgroup of patients with nonischemic DCM and suggests that left bundle branch block may be the causal factor of DCM in this subgroup of patients.     

Pathophysiologic significance of “stress” or relative polycythemia in essential hypertension

Fourteen patients with essential hypertension (blood pressure 167 ± 2/106 ± 2 [mean ± standard error of the mean] mm Hg) were studied prospectively to determine the pathophysiologic correlates of their “stress” or relative polycythemia. All patients had a high hematocrit level (53.1 ± 0.4 vol percent), contracted plasma volume (16.2 ± 0.4 ml/cm height) and normal red cell mass and serum erythropoietin levels. Blood and plasma viscosity (0.076 ± 0.005 and 0.017 ± 0.001 poise, respectively) were increased, and plasma renin activity in the supine, resting state averaged 1.8 ± 0.3 ng/ml per hour. All patients were treated with methyldopa to achieve normal arterial pressure and the previous determinations were repeated after 1 and 4 weeks of treatment. Reduction of pressure was associated with expansion of plasma volume (P < 0.001) and significant decreases in hematocrit, blood and plasma viscosity and resting plasma renin activity (P < 0.001). Red cell mass and serum erythropoietin levels remained unchanged. Therefore, the so-called stress polycythemia is a pathophysiologic manifestation of the hypertensive vascular disease in which the abnormal hemodynamic and rheologic alterations can be reversed by antihypertensive therapy. The significance of this reversal may have some bearing upon the high prevalence rates of severe cardiovascular complications associated with so-called stress polycythemia and high renin essential hypertension.     

How Do Physicians Define “Light,”“Moderate,” and “Heavy” Drinking?

Although widely used, terms associated with consumption of alcohol–such as "light,""moderate," and "heavy"—are unstandardized. Physicians conveying health messages using these terms therefore may impart confusing information to their patients or to other physicians. As an initial attempt to assess if informal standardization exists for these terms, the present study surveyed physicians for their definitions of such terms. Physicians operationally defined "light" drinking as 1.2 drinks/day, "moderate" drinking as 2.2 drinks/ day, and "heavy" drinking as 3.5 drinks/day. Abusive drinking was defined as 5.4 drinks/day. There was considerable agreement for these operational definitions, indicating there is indeed an informal consensus among physicians as to what they mean by these terms. Gender and age did not influence these definitions, but self-reported drinking on the part of physicians was a factor. We also asked physicians for their opinions regarding the effects of "light,""moderate," and "heavy" drinking on health in general and specifically on health-related implications for pregnant women, and whether they felt their patients shared these beliefs.     

A point mutation in the iron-responsive element of the L-ferritin in a family with hereditary hyperferritinemia cataract syndrome.

BACKGROUND: Hereditary hyperferritinemia cataract syndrome is an autosomal dominant condition that is characterized by a high serum ferritin level and bilateral early-onset cataracts in the absence of iron overload. The genetic abnormality is identified as a mutation in the 5' regulatory region of the L-ferritin messenger RNA known as the iron-responsive element (IRE). The IRE controls ferritin synthesis in response to cytoplasmic iron pools by interacting with regulatory proteins called iron responsive proteins. Mutations in the IRE decrease its affinity for iron responsive proteins, leading to the constitutive synthesis of L-ferritin which results in hyperferritinemia and the intracellular accumulation of ferritin in the lens and eventual cataract formation. PATIENTS AND METHODS: A 22-year-old woman who was being investigated for hyperferritinemia was diagnosed with hereditary hyperferritinemia cataract syndrome after an extensive workup, including genetic testing for hemochromatosis and a liver biopsy to rule out iron overload. She developed anemia with phlebotomy treatments and subsequently developed symptomatic cataracts. The pedigree of her family affected with cataracts was consistent with an autosomal dominant transmission pattern. DNA was extracted from peripheral leukocytes of eight family members, four of whom were affected by cataracts. Polymerase chain reaction amplification of the 5' region of the L-ferritin gene was performed and a heterozygous point mutation (G32T) was identified in the bulge region of the IRE. CONCLUSION: The combination of early-onset cataracts and an elevated ferritin level should suggest this genetic syndrome.