INTRODUCTION Hypertension is one of the most studied risk factors for cardiovascular disease in adults; in children and adolescents, its global prevalence changes with age, from 1%–3% in children to 3.2% in adolescents. In adults, in addition to hypertension, several biochemical markers of cardiovascular risk have been identified. Confirming an association between these and hypertension in childhood and adolescence would allow for more timely diagnosis and monitoring of cardiovascular disease, since the presence of both the markers and hypertension would imply increased risk.  

OBJECTIVE Confirm an association between biochemical risk markers of cardiovascular disease and hypertension in children aged 8 to 11 years.

METHODS A cross-sectional study of 373 children aged 8–11 years was conducted in 3 primary schools in the city of Santa Clara in central Cuba. The variables examined were age, sex, height, blood pressure, cholesterol, triglycerides, lipoproteins and apolipoproteins. The children were classified as normotensive, prehypertensive or hypertensive, based on blood pressure readings and percentiles for age, sex and height. Descriptive statistics were calculated for quantitative variables. A bivariate analysis, tests of independence for qualitative variables and a means comparison for quantitative variables (ANOVA and its nonparametric alternative, the Kruskal Wallis test) were performed. Fisher’s F-test and its associated probability value were employed.

RESULTS Some 32.2% of the children were prehypertensive and 5.1% hypertensive. Cholesterol and triglyceride values were significantly higher in hypertensive than in normotensive children (p = 0.028 and p = 0.047, respectively). HDL numbers were higher in normotensive children (p =0.001), and LDL numbers and the LDL/HDL ratio were higher in the hypertensive children, with differences between groups (p = 0.001 for both variables). There were differences between the three blood pressure categories for lipoprotein(a) and ApoA (p <0.001 and p = 0.001), for ApoB and for the ApoB/ApoA ratio (p <0.001 for both variables), with lower ApoA values and higher ApoB and ApoB/ApoA values in the hypertensive children.

CONCLUSIONS The biochemical risk markers most strongly associated with hypertension in children are ApoB values, LDL, lipoprotein(a), and LDL/HDL and ApoB/ApoA ratios.

KEYWORDS Adolescent, child, hypertension, apolipoproteins, cardiovascular diseases, risk factors, Cuba

INTRODUCTION Many clinical settings lack the necessary resources to complete angiographic studies, which are commonly used to predict complications and death following acute coronary syndrome. Corrected QT-interval dispersion can be useful for assessing risk of myocardial infarction recurrence.

OBJECTIVE Evaluate the relationship between corrected QT-interval dispersion and recurrence of myocardial infarction in patients with ST-segment elevation.

METHODS We conducted a prospective observational study of 522 patients with ST-segment elevation myocardial infarction admitted consecutively to the Camilo Cienfuegos General Provincial Hospital in Sancti Spiritus, Cuba, from January 2014 through June 2017. Of these, 476 were studied and 46 were excluded because they had other disorders. Demographic variables and classic cardiovascular risk factors were included. Blood pressure, heart rate, blood glucose, and corrected and uncorrected QT-interval duration and dispersion were measured. Patients were categorized according to the Killip-Kimball classification. Association between dispersion of the corrected QT-interval and recurrence of infarction was analyzed using a binary logistic regression model, a regression tree and receiver operator characteristic curves.

RESULTS Patients with recurrent infarction (56; 11.8%) had higher average initial blood glucose values than those who did not have recurrence; the opposite occurred for systolic and diastolic blood pressure and for left ventricular ejection fraction. Dispersion of the corrected QT-interval was a good predictor of infarction recurrence according to a multivariate analysis (OR = 3.09; 95% CI = 1.105–8.641; p = 0.032). Cardiac arrest is the variable that best predicts recurrence. No recurrence of infarction occurred in 97% of patients without cardiac arrest, left ventricular ejection fraction >45% and corrected QT-interval dispersion <80 ms.

CONCLUSIONS Risk of infarction recurrence is low in patients without cardiac arrest, with left ventricular ejection fraction >45% and with dispersion of corrected QT-interval <80 ms. Patients with corrected QT-interval dispersion ≥80 ms have greater risk of recurrence of infarction, which suggests that this variable could be used for stratification of risk following ST-segment elevation myocardial infarction.

KEYWORDS ST-elevation myocardial infarction, myocardial infarction, electrocardiography, chronic disease, risk assessment, Cuba

Over 400 delegates from 28 countries gathered recently in Havana for the 2nd Pan-American Congress of Physiological Sciences (May, 2019). It was quite an event, the level of science attesting to the quality of participants from the world over. The conference attracted more US scientists to Cuba than any other in the field of medicine […]

Translated from Spanish and reprinted with permission from Revista Cubana de Salud Pública Vol 44 No 2, Apr–Jun 2018. Original available from: http://www.revsaludpublica.sld.cu/index.php/spu/article/view/1065

The process of research and evaluation of new products and technologies requires a combination of transdisciplinary theoretical and methodological approaches for managing and achieving objectives. The research, development and evaluation strategy of the new Cuban pneumococcal vaccine combines the approaches of team science and accelerated vaccine introduction. These frameworks are proposed for discussions regarding biotech product evaluation, using their application to the Pneumococcus Project as an example. Emphasis is on the use of team science to eliminate obstacles to obtaining a product of great scientific and technological complexity while establishing robust scientific evidence to support its use and marketing. All of this is in support of opportune and efficient decisions for accelerated introduction of new vaccines in Cuba.

KEYWORDS Team science, vaccines, pneumococcal conjugate vaccine, Cuba

Pleural effusion is a common condition in critically ill patients (both clinical and surgical). Its diagnosis and classification are important for followup of patients with cardiorespiratory difficulty. Lung ultrasound is used for this purpose, but no reports have been published on its use in Cuba with critically ill patients in intensive care units. We performed lung ultrasound on 144 such patients with cardiorespiratory illnesses, average age 54 years, predominantly men (66%; 95/144), with average APACHE II score 13.6, and 22.1% mortality risk. Patients were divided into two groups: clinical (bronchopneumonia and cardiac insufficiency) and surgical (postoperative liver and kidney transplant or vascular and cardiovascular surgery) to diagnose and classify pleural effusion according to locus (right, left and bilateral) and structural pattern (I, II A, II B, III and IV). Pleural effusions were diagnosed in 81.2% (117/144) of patients (clinical 44.4%, 52/117; surgical 55.6%, 65/117). Bilateral location was the most common (68.4%, 80/117), followed by right (23.9%, 28/117) and then left (7.7%, 9/117). Structural pattern I (anechoic appearance) was observed in 61.5% of cases (72/117); 21.4% (25/117) were II A, 12.8% (15/117) II B, 3.4% (4/117) III, and 0.9% (1/117) were IV. We found no association between pleural effusion localization and ultrasound structural pattern in clinical patients (Fisher exact test 4.2 p = 0.9). In surgical patients, however, complex ultrasound patterns (II A, II B and III) were significantly more common in bilateral forms (Fisher exact test 14.1; p = 0.009). Further studies of this type in Cuba will help provide useful data for prompt treatment and followup of these patients.

KEYWORDS Pleural effusion, critical illness, intensive care unit, lung ultrasound, diagnostic ultrasound, Cuba

The first 1000 days of life constitute a short and exceptionally important period when the foundation is established for children’s growth, development and lifelong health. Cuba has a comprehensive care system for this population that aims to promote the best start in life so that children can reach their highest development potential. This is carried out through the national public health and education systems and also includes elements of health protection, prevention of harm and disease and social welfare for children.

Cuba’s infant mortality rate has remained <5 deaths per 1000 live births for 10 consecutive years, and in 2017 reached 4 per 1000, the lowest rate to date. The mortality rate for children aged <5 years in 2017 was 5.5 per 1000 live births, with a survival rate of 99.5%; low birth weight was 5.1% and vaccination coverage >95%. Among children aged 1 year in Cuba’s Educate Your Child program in 2014, >90% met age-specific indicators in all four developmental domains (intellectual, motor, socioaffective and language). Cuba has universal coverage for antenatal care and, in 2017, 99.9% of births occurred in health institutions. All working mothers receive paid antenatal leave from 34 weeks of gestation, continued through the child’s first year, to facilitate breastfeeding and child care. In 2018, the Cuban government allocated 27% of its national budget to health and social welfare and 21% to education.

KEYWORDS Growth and development, child development, child health services, preventive health services, primary health care, pregnant women, children, child rearing, intersectoral collaboration, Cuba

Ibraín E. Corrales-Reyes DDS, Yasmany Fornaris-Cedeño, Alberto J. Dorta-Contreras MS PhD, Christian R. Mejia MD MS PhD, Josmel Pacheco-Mendoza DVM MS, Ricardo Arencibia-Jorge PhD

INTRODUCTION The steadily increasing prevalence of diabetes globally has captured researchers’ attention. Cuban production of scientific articles on diabetes has not been studied from a bibliometric perspective.

OBJECTIVE Characterize the production and impact of research and review articles on diabetes by Cuban authors in journals listed in the Scopus bibliographic database, as well as related collaboration among Cuban institutions and between Cuban and non-Cuban institutions.

METHODS A bibliometric analysis was conducted using 2000–2017 data from the Scopus database. The following search strategy was used: descriptor (diabetes), country (Cuba), publication source (journal), article type (original research, review article). Bibliographic indicators of production, visibility, impact and collaboration were examined.

RESULTS Cuba contributed 3.2% of Latin American production and 0.1% of global production related to diabetes. Within Cuba’s scientific production (610 articles, 538 original research and 72 review), 85.9% had a Cuban corresponding author (Cuban leadership). In articles with international collaboration (22.9%), however, most (67.9%) had non-Cuban corresponding authors. A total of 47% (287) were articles involving a single institution. Only 11.1% were published in top-ranked journals, and 14.4% were cited >10 times. Cubans were lead authors on 0.3% of the most frequently cited (top 10%) articles on diabetes in Scopus. A total of 38.4% of this production appeared in low-impact journals and 57.9% in Cuban journals.

Articles published in English accounted for 30% of total and obtained higher impact in terms of citations than articles in Spanish. The strongest networks for scientific collaboration were those that connected Cuban and US researchers.

CONCLUSIONS Cuban scientists conduct research on diabetes, but their work is not highly visible in the peer-reviewed literature, particularly in top-ranked journals. The problem is not simply one of publishing more, but of knowing how and where to publish. It is urgent that Cuban universities training health professionals at all levels include instruction on scientific writing.

KEYWORDS Diabetes, health services research, scientific journals, bibliometrics, Cuba

INTRODUCTION The consequences of de novo balanced structural chromosome aberrations diagnosed antenatally are unpredictable, and, as a result, they introduce uncertainty into genetic counseling decisions.

OBJECTIVE Describe de novo balanced structural aberrations present at antenatal diagnosis in samples from pregnant women in five Latin American countries and determine their effect on carrier individuals.

METHODS This was a retrospective observational study based on analysis of 109,011 antenatal tests conducted from January 1981 to December 2016 in Cuba, Uruguay, Costa Rica, Mexico, and Colombia. Thirteen cytogenetic laboratories provided information that included the cases analyzed during the study period; number of de novo balanced structural aberrations diagnosed antenatally; number of diagnoses with de novo balanced structural aberrations that resulted in termination of pregnancy; detailed descriptions of the karyotypes of de novo balanced structural aberration carriers, and descriptions of the form of diagnosis, including types of samples used (amniotic fluid, chorionic villus or fetal blood). Each laboratory also provided pathology reports and genetic counseling at time of diagnosis. Postnatal followup for pregnancies carried to term continued for at least two years.

RESULTS Of the 109,011 antenatal tests studied, 72 (0.07%) showed de novo balanced structural aberrations. These events primarily involved chromosomes 1, 2, 7, 14, 18, and 20. Of the 79 breakpoints identified, the most common were 5p15.3, 7q11.2, 7q22, and 14q24. We identified three breakpoints corresponding to 3.8% (3q13.1, 3q13.2, and 9p12) that were not reported in other studies of de novo balanced structural aberrations diagnosed antenatally in patients from other geographic regions or in studies of chromosomal fragile sites. Two of these breakpoints (3q13.1 and 3q13.2) were associated with high risk of phenotypic abnormalities. Information on antenatal or postnatal followup was available for 62 (86%) of de novo balanced structural aberration carriers; of the 44 carriers with postnatal followup, 10 had phenotypic abnormalities.

CONCLUSIONS Three new de novo breakpoints were identified, presumably related to genetic admixture characteristics in Latin America. Since some diseases associated with de novo balanced structural aberrations detected antenatally have a late onset, followup for at least two years is recommended for carriers of these aberrations. The information in this study is useful in genetic counseling for pregnant women in Latin America.

KEYWORDS Antenatal diagnosis, prenatal diagnosis, antenatal screening, chromosomal aberrations, chromosomal breakpoints, pregnancy, Colombia, Costa Rica, Cuba, Mexico, Uruguay, Latin America

Public health systems face the contradiction of skyrocketing cancer incidence and cancer drug prices, thus limiting patient access to more effective treatments. The situation is particularly dire in low- and middle-income countries. We urgently need consensus on the main determinants of this problem, as well as specific, effective and feasible solutions.

Analysis of available data reveals that the problem has reached its current magnitude only recently and is not related to the growing complexity of drug production technology, but rather to corporate profits and the failure of market mechanisms to allocate resources based on health needs.

Despite the obstacles, there is ample room for effective intervention: joint price negotiations, cost transparency, greater support for creation of manufacturing capacity, and regulatory measures that facilitate introduction of generic and biosimilar drugs and reduce intellectual property barriers to better use of flexibilities in the Agreement on Trade-Related Aspects of Intellectual Property Rights.

Such actions will not be effective if there is no consensus around them, or if low- and middle-income countries act in isolation. This is precisely where international organizations must intervene.

KEYWORDS Public health, price, cancer drugs, inequality, less-developed countries, developing countries, Cuba

He was born in Chicago, Illinois, USA, but his family is Cuban. After 1959, they returned to the island, where Dr Mitchell Valdés received his medical degree at the University of Havana in 1972. He went on to study clinical neurophysiology, earning his PhD with a dissertation on the auditory system’s sensory physiology. When the Neuroscience Center opened (as part of western Havana’s Scientific Pole). he became its director, a post he holds today. Dr Valdés, a Distinguished Member of the Cuban Academy of Sciences, is widely published and has collaborated with colleagues in dozens of countries, including the USA, UK, Italy and Holland. He is a full professor of clinical neurophysiology, sits on Cuba’s National Coordinating Group for Persons with Disabilities, and serves as an honorary professor at the University of Illinois at Chicago. What brought me to his office is the set of symptoms reported by some two dozen US diplomats in Cuba and more recently in China as well. And the controversy surrounding what might be the root cause—a topic that has crossed the line from medicine into politics. MEDICC Review’s intent was to hear from Dr Valdés on the science pertinent to the controversy.

INTRODUCTION Flow cytometry allows immunophenotypic characterization of important lymphocyte subpopulations for diagnosis of diseases such as cancer, autoimmune diseases, immunodeficiencies and some infections. Normal values of rare lymphoid cells in blood, quantified by cytometry, vary among different populations; so it is indispensable to obtain normal national values that can be used in clinical practice.

OBJECTIVE Characterize distribution of rare T-lymphocyte populations in peripheral blood, specifically double-positive T, natural killer T and activated T lymphocytes, as well as their relationship to sex and age.

METHODS A cross-sectional study was carried out in 129 adults (68 women, 61 men) aged >18 years, without chronic diseases or unhealthy habits, who signed informed consent. Peripheral blood was collected for immunophenotyping of lymphocyte subpopulations with monoclonal antibodies specific for CD4+CD8+ double-positive T cells, CD3+CD56+ natural killer T cells, and CD3+CD25+HLA-DR+ activated T cells. An eight-color flow cytometer (Beckman Coulter Gallios) was used. The analytic strategy was modified, associating variables of interest in a single graphic, using conventional monoclonal labeling antibodies. Medians and minimum and maximum percentiles (2.5 and 97.5, respectively) were used as descriptive statistics, stratified by sex, for cell counts and percentages. A linear regression model was applied to assess age effects and a two-tailed Mann-Whitney U test for independent samples was used to assess sex differences. The significance threshold was set as p ≤0.05.

RESULTS Median percentages of total lymphocytes: natural killer T cells 6.3% (1.4%–23%) in men and 4.7% (0.8%–11.3%) in women (p = 0.003); activated T cells 1.0% (0.2%–2.2%) in men and 1.2% (0.4%–3.1%) in women, without statistical significance; and double positives 0.8% (0.1%–4.2%) in men and 0.9% (0.3–5.1) in women, also without statistical significance. Median cell counts (cells/mL) were: natural killer T cells, 126 (27–580) in men and 105 (20–279) in women (p = 0.023); activated T cells: 20 (4–46) in men and 25 (7–75) in women, (p = 0.013) and double-positive T cells: 17 (2–85) in men and 21 (7–154) in women, without statistical significance. Sex influenced natural killer T cells, but age did not.

CONCLUSIONS Age does not affect counts and percentages of rare T lymphocyte subpopulations in the blood of healthy Cuban adults. Sex differences found for some phenotypes suggest the need for different reference values for women and men.

KEYWORDS Normal values, T-lymphocyte subpopulations, flow cytometry, Cuba

Cristian Morales, an economist by training, has dedicated his career to improving health and health equity in the Americas through his work with PAHO/WHO. This has taken him from floods and earthquakes in Haiti to PAHO’s Washington DC offices, where he was instrumental in achieving consensus on a resolution aiming for universal health—coverage plus access—approved by all governments in the Americas. Since 2015, he has served as PAHO/WHO Permanent Representative in Cuba and has recently been appointed to the analogous post in Mexico. At the end of his three years in Havana, MEDICC Review talked with Dr Morales about his experience, the Cuban health system, and the values it shares with the organization he represents. This is part one of the interview, the second part to be published in our January 2019 issue, in which we’ll talk more about the health system in Cuba itself, its achievements and also its challenges.

INTRODUCTION Serogroup B meningococcal outer membrane vesicle vaccines have been effective against vaccine-type strains, but their effectiveness against heterologous strains has been controversial. The Cuban VA-MENGOC-BC vaccine is of this type, but also includes meningococcus C capsular polysaccharide.

OBJECTIVES Assess the effectiveness of VA-MENGOC-BC in reducing meningococcal disease caused by homologous or heterologous serogroup B strains and its serological effectiveness against meningococcus C.

METHODS A review of studies of VA-MENGOC-BC’s application in Cuba, Brazil, Uruguay and Colombia was carried out to examine the vaccine’s effectiveness in reducing meningococcal disease during serogroup B outbreaks. Serological effectiveness against serogroup C determined in these studies (indicated by bactericidal antibody titers before and after vaccination) was also analyzed.

RESULTS VA-MENGOC-BC’s effectiveness against homologous serogroup B strains has consistently been greater than 80% in all age groups. Effectiveness in heterologous contexts was also above 80% in individuals aged >4 years. Lower effectiveness in heterologous contexts was found in Brazilian children aged <2 years, although still >50%. Effectiveness increased when assessed based on mortality rates, as well as in cases of clinically severe meningococcal disease. The carrier-state pattern was modified after vaccination with reduction of hypervirulent lineages. Some 60% of infants (aged <1 year) attained protective bactericidal antibody titers against serogroup C. Higher protection rates were achieved in older children.

CONCLUSIONS In addition to prevention of meningococcal disease caused by homologous serogroup B strains, VA-MENGOC-BC should be considered for heterologous contexts. It is protective against serogroup C in all age groups.

KEYWORDS Neisseria meningitidis, meningococcal disease, meningococcal vaccines, serogroup B meningococcus, serogroup C meningococcus, immunogenicity, bacterial outer membrane proteins, heterologous effects of vaccines, acellular vaccines, Cuba

INTRODUCTION Mortality analysis based on a single cause of death is not, in most cases, fully informative. There are several more illuminating procedures using a multiple cause of death approach; these are little known and rarely used in Cuba. The simplest of these methods, while methodologically limited, consists of summing all deaths from a specific cause mentioned on death certificates, regardless of whether the cause is listed as underlying or contributing.

OBJECTIVE Using Cuban data, critically assess and implement two of the most recognized approaches to analyzing multiple causes of death.

METHODS Multiple causes of death in Cuba were assessed for the years 2005, 2010 and 2015, employing death records from the National Medical Records and Health Statistics Bureau of Cuba’s Ministry of Public Health. With the example of diabetes mellitus as underlying cause, we explored connections between underlying and associated (antecedent and contributing) causes on death certificates using two approaches from the international literature: the simple method and the cause-of-death association indicator.

RESULTS The study identified main trends in multiple causes of death identified in 2005, 2010 and 2015, overall and by age group and sex. We observed a trend to increasing mean number of causes of death per death certificate between 2005 and 2015. The number of causes reported showed no substantial differences by age group or sex. Diseases of the arteries, arterioles and capillaries were by far the most frequently associated with diabetes mellitus as underlying cause.

CONCLUSIONS The multiple causes of death approach affords more nuanced understanding of patterns of disease, comorbidity and death in the Cuban population. The indicators used fulfill different roles: the simple method brings to light the full range of ways in which a given cause contributes to mortality, and the cause-of-death association indicator enables exploration of links between different causes of death, not possible with the simple method.

KEYWORDS Mortality, multifactorial causality, causes of death, diabetes mellitus, Cuba

INTRODUCTION By the end of 2017, there were more than 28,000 individuals living with HIV in Cuba, over 80% receiving antiretroviral therapy, which dramatically reduces viral replication, improves immune status and decreases risk of transmission. These results could be jeopardized by emergence of HIV-1 drug resistance. In 2009, a test for HIV-1 genotypic resistance was introduced in routine clinical practice in Cuba.

OBJECTIVE Investigate antiretroviral resistance and its relation to subtype distribution in HIV-1 treatment-naïve and previously treated patients in Cuba.

METHODS Resistance and HIV-1 subtype distribution were determined in 342 antiretroviral treatment-naïve patients and 584 previously treated for HIV-1 whose blood specimens were sent to the Pedro Kourí Tropical Medicine Institute during 2009–2014. Transmitted drug resistance was determined using the Calibrated Population Resistance Tool v.6. Drug resistance analysis was conducted using the algorithm Rega v9.1.0.

RESULTS Prevalence of transmitted drug resistance was 11.4%, and 41% of mutated viruses exhibited dual-class resistance to nucleoside reverse transcriptase inhibitor and non-nucleoside reverse transcriptase inhibitor. Overall, 84.9% of patients had ≥1 resistance mutation, 80% had ≥1 nucleoside reverse transcriptase inhibitor mutation, 71.4% had ≥1 non-nucleoside reverse transcriptase inhibitor mutation and 31.7% had ≥1 protease inhibitor mutation. K65R and K101E mutations were significantly more frequent in subtype C, L210W in CRF19_cpx, and M47V/I in CRF BGs (20, 23, 24). Full class resistance to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors and multidrug resistance were detected in 21.2%, 32.4%, 8% and 4.1% of patients, respectively. Average percentage resistance to nucleoside reverse transcriptase inhibitor, protease inhibitor, full class resistance to nucleoside reverse transcriptase inhibitor, protease inhibitor and multidrug resistance increased in patients failing two or more regimens. Nevertheless, after 2011, a declining trend was observed in the frequency of multidrug resistance and full class resistance to nucleoside reverse transcriptase inhibitors and protease inhibitors.

CONCLUSIONS Detected levels of transmitted drug resistance highlight the need for a national surveillance study in treatment-naïve patients. Resistance prevalence is high in previously treated patients but appears to be decreasing over time. The frequency of resistance mutations in recombinant forms of HIV in Cuba needs further study.

KEYWORDS Antiretroviral therapy, highly active antiretroviral therapy, HIV, anti-HIV agents, drug resistance, multiple drug resistance, Cuba

INTRODUCTION Diabetic foot ulcers are a chronic complication in patients with diabetes mellitus. They appear as a result of the combination of diabetic polyneuropathy and angiopathy, and in many cases require amputation of the affected extremity. Clinical trials have demonstrated that repeated local infiltration with Heberprot-P can improve healing of chronic diabetic foot ulcers. Although there is evidence of its effects as a granulation stimulator and on cell migration and proliferation, genetic control mechanisms explaining its anti-inflammatory and oxidative stress reduction properties are not yet thoroughly understood.

OBJECTIVE Analyze changes in expression of genes involved in healing after treatment of diabetic foot ulcers with Heberprot-P.

METHODS Biopsies were collected from diabetic foot ulcers of 10 responding patients before and after 2 weeks’ treatment with Heberprot-P (75-μg applied intralesionally 3 times per week). Total RNA was obtained and quantitative PCR used to determine expression of 26 genes related to inflammation, oxidative stress, cell proliferation, ngiogenesis and extracellular matrix formation. Genetic expression was quantified before and after treatment using REST 2009 v2.0.13.

RESULTS After treatment, there was a statistically significant increase in expression of genes related to cell proliferation, angiogenesis and formation of extracellular matrix (PDGFB, CDK4, P21, TP53, ANGPT1, COL1A1, MMP2 and TIMP2). A significant decrease was observed in gene expression related to inflammatory processes and oxidative stress (NFKB1, TNFA and IL-1A).

CONCLUSIONS Our findings suggest that Heberprot-P’s healing action on diabetic foot ulcers is mediated through changes in genetic expression that reduce hypoxia, inflammation and oxidative stress, and at the same time increase cell proliferation, collagen synthesis and extracellular matrix remodeling. The kinetics of expression of two genes related to extracellular matrix formation needs further exploration.

KEYWORDS Epidermal growth factor, EGF, diabetic foot ulcer, wound healing, quantitative real-time PCR, gene expression, Cuba