Spontaneous Coronary Artery Dissection as a Cause of Acute Myocardial Infarction in COVID-19 Patients: A Case Report and Review of the Literature.

Patients with COVID-19 often experience significant cardiovascular complications, including heart failure, myocarditis, and acute coronary syndrome. We present the case of a male patient with severe COVID-19 pneumonia, complicated with inferior ST-segment elevation myocardial infarction (STEMI), which was attributed to spontaneous coronary artery dissection (SCAD). We also make a review of the literature on case reports of patients with COVID-19 and acute myocardial infarction due to SCAD. Through these clinical cases, a potential correlation between SCAD and COVID-19 infection is implied. Endothelial dysfunction, thrombotic complications, and disturbance of the vascular tone are established COVID-19 sequelae, triggered either by direct viral injury or mediated by the cytokines' storm. These abnormalities in the coronary vasculature and the vasa vasorum could result in SCAD. Moreover, disturbances of the vascular tone can cause coronary vasospasm, a reported precipitant of SCAD. Thus, SCAD should be considered in COVID-19 patients with acute coronary syndrome (ACS), and in the case of STEMI, an early angiographic evaluation, if feasible, should be performed rather than thrombolysis to avoid potential adverse events of the latter in the setting of SCAD.

Seasonality and Objective Physical Activity and Sedentary Behaviour among Older Adults from Four European Countries.

OBJECTIVE: The present study aimed to explore the relationship between objective physical activity and sedentary behaviour with seasonality among a sample of older adults living in four European countries. METHODS: A sample of 169 older adults living in Croatia, Greece, Portugal, and Poland (mean age = 72.2 ± 6.0, 68% female) had valid objective physical activity and sedentary behaviour data collected in different seasons of the year: spring and autumn/winter. Physical activity and sedentary behaviour were collected with accelerometers (ActiGraph, GT3X), over 7 consecutive days, in both periods. A valid record was defined as at least two weekdays and one weekend day with 10 hours of wearing time. Analyses were performed with IBM SPSS 28.0, using t-test, ANOVA, and binary logistic regressions. RESULTS: Most older adults from the four countries met the physical activity guidelines in spring and autumn/winter. No significant variations were found across seasons for sedentary behaviour and physical activity both for light and vigorous intensity, regardless of sex, country, education, and body mass index (BMI). A decline in moderate physical activity intensity from spring to autumn/winter was found for those with lower education and higher BMI. CONCLUSION: The promotion of physical activity must be considered in programs to promote healthy aging throughout the year, especially considering the moderate intensity and those populations with higher BMI and lower educational levels.

Mechanisms of Atrial Fibrillation: How Our Knowledge Affects Clinical Practice.

Atrial fibrillation (AF) is a very common arrhythmia that mainly affects older individuals. The mechanism of atrial fibrillation is complex and is related to the pathogenesis of trigger activation and the perpetuation of arrhythmia. The pulmonary veins in the left atrium arei confirm that onfirm the most common triggers due to their distinct anatomical and electrophysiological properties. As a result, their electrical isolation by ablation is the cornerstone of invasive AF treatment. Multiple factors and comorbidities affect the atrial tissue and lead to myocardial stretch. Several neurohormonal and structural changes occur, leading to inflammation and oxidative stress and, consequently, a fibrotic substrate created by myofibroblasts, which encourages AF perpetuation. Several mechanisms are implemented into daily clinical practice in both interventions in and the medical treatment of atrial fibrillation.

Effect of vildagliptin on hsCRP and arterial stiffness in patients with type 2 diabetes mellitus.

OBJECTIVE: To evaluate the effect of dipeptidyl-peptidase-4 (DPP-4) inhibitor vildagliptin on high sensitivity C-reactive protein (hsCRP) and arterial stiffness (AS) in patients with type 2 diabetes (T2DM). DESIGN: Sixty-four drug-naive diabetic patients, with inadequate glycemic control, participated in this randomized, open-label study. Half of the patients received metformin 1700 mg/d and the other half of them received metformin 1700 mg/d plus vildagliptin 100 mg/d. AS was measured by carotid-femoral Pulse Wave Velocity (cfPWV). Body weight (BW), body mass index (BMI), blood pressure (BP), hsCRP, glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), lipid profile, albumin/creatinine ratio (ACR), fasting insulin, C-peptide, homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of ß-cell function (HOMA-ß) were also assessed at baseline and after 6 months. RESULTS: Vildagliptin in combination with metformin had a beneficial influence on hsCRP, HbA1c, C-peptide and HOMA-ß index (p <0.05) but had no effect on cfPWV, BP, BW, BMI, lipid profile, ACR and HOMA-IR compared with metformin alone (p=NS). CONCLUSIONS: We have found that the addition of vildagliptin to metformin for a period of six months decreased hsCRP, improved glycemic control and ß-cell function but had no effect on AS in drug-naive patients with T2DM.

Left ventricular systolic and diastolic function in normotensive type 2 diabetic patients with or without autonomic neuropathy: a radionuclide ventriculography study.

We investigated the relation between diabetic autonomic neuropathy (DAN) and left ventricular (LV) function in 59 patients with type 2 diabetes mellitus (T2DM) free of coronary artery disease (CAD) or hypertension. Diabetic autonomic neuropathy was established by ≥2 abnormal autonomic nervous function tests. Left ventricular systolic and diastolic functions were assessed by resting radionuclide ventriculography. Compared with non-DAN patients (n=24), patients with DAN (n=35) had an increased adjusted atrial contribution to ventricular filling (A/V%, 30.1%±8.2% vs 26.5%±5.1%; P=.031), suggestive of diastolic dysfunction (DD). There were no differences between the 2 groups in peak filling rate, first 1/3 filling fraction, ejection fraction, cardiac output, and cardiac index. Patients with diabetic autonomic neuropathy had an increased heart rate (77.8±6.3 vs 69.3±3.3 bpm; P<.0001) and a higher rest LV workload (10,072±1165 vs 8606±1075 bpm mm Hg; P<.0001). Patients with DAN T2DM without CAD or hypertension have DD, increased A/V index, and a higher LV working load than non-DAN patients.

Steroidal esters of the aromatic nitrogen mustard 2-[4-N,N-bis(2-chloroethyl)amino-phenyl]butanoic acid (2-PHE-BU): synthesis and in-vivo biological evaluation.

On the basis of the results of in-silico predictions and in an effort to extend our structure-activity relationship studies, the aromatic nitrogen mustard 2-[4-N,N-bis(2-chloroethyl) amino-phenyl]butanoic acid (2-PHE-BU) was synthesized and conjugated with various steroidal alcohols. The resulting steroidal esters were evaluated for their in-vivo toxicity and antileukemic activity in P388-leukemia-bearing mice. The new derivatives showed significantly reduced toxicity and marginally improved antileukemic activity compared with free 2-PHE-BU. Nevertheless, they did not prove to be superior either to the template steroidal ester used for in-silico predictions or to previously synthesized steroidal esters of aromatic nitrogen mustards. The results obtained indicate that in-silico design predictions may guide the design and synthesis of new bioactive steroidal esters, but further parameters should be considered aiming at the discovery of compounds with optimum activity.

Saffron as a source of novel acetylcholinesterase inhibitors: molecular docking and in vitro enzymatic studies.

Inhibitors of acetylcholine breakdown by acetylcholinesterase (AChE) constitute the main therapeutic modality for Alzheimer's disease. In the search for natural products with inhibitory action on AChE, this study investigated the activity of saffron extract and its constituents by in vitro enzymatic and molecular docking studies. Saffron has been used in traditional medicine against Alzheimer's disease. Saffron extract showed moderate AChE inhibitory activity (up to 30%), but IC(50) values of crocetin, dimethylcrocetin, and safranal were 96.33, 107.1, and 21.09 µM, respectively. Kinetic analysis showed mixed-type inhibition, which was verified by in silico docking studies. Safranal interacts only with the binding site of the AChE, but crocetin and dimethylcrocetin bind simultaneously to the catalytic and peripheral anionic sites. These results reinforce previous findings about the beneficial action of saffron against Alzheimer's disease and may be of value for the development of novel therapeutic agents based on carotenoid-based dual binding inhibitors.

In silico/in vitro study of hybrid D-modified steroidal alkylator anticancer activity using uridine phosphorylase as target protein.

BACKGROUND: In order to reduce toxicity and to enhance anticancer activity of nitrogen mustards, three hybrid steroidal esters were synthesized and tested in vitro against human pancreatic cancer cells expressing uridine phosphorylase (UPase). The inhibition potency against a target protein implicated in the chemotherapy of solid tumors, such as UPase, is of fundamental importance in the design and synthesis of new anticancer drugs. MATERIALS AND METHODS: MTT colorimetric assay and molecular docking were employed for the in vitro and in silico drug evaluation, respectively. RESULTS: A difference in cell sensitivity was found, which followed the known different UPase expression in the cell lines. Molecular docking studies on UPase protein, revealed the tested compounds to be bound to the binding cavity of the protein, with different affinity. Between the two D-modified compounds, the D-homo-aza (lactam)-hybrid compound (C2) was found to interact with the protein in a more efficient way. CONCLUSION: The molecular docking data were in accordance with the in vitro results, where the lactam steroid alkylator showed significantly higher cytostatic and cytotoxic activity than the non-D-modified compounds, which also correlated with the level of UPase expression in the pancreatic cancer cells.

Antitumour and cytogenetic effects of modified steroidal derivatives of propenoic acid: in vivo/in vitro studies.

BACKGROUND: Modified steroidal derivatives (PK11-PK14) of p-bis(2-chloroethyl)aminophenyl propenate (PK15) were used to study their antitumour activity on Lewis lung carcinoma (LLC) and their effect on sister chromatid exchanges (SCEs) and human lymphocyte proliferation kinetics. MATERIALS AND METHODS: LLC was tested in this study. C57BL mice were used for in vivo chemotherapy evaluation and the antitumour activity was assessed. Lymphocyte cultures were used to study the genotoxic effect in vitro. RESULTS: PK15 and PK11 were the most effective against LLC, causing significant inhibition of tumour growth. PK11 and PK15 induced significant increase in SCE rates. A correlation was observed between the cytogenetic effect and the antitumour effectiveness. CONCLUSION: The order of the antitumour effectiveness of PK11-PK15 resembled the order of the cytogenetic damage induced by the same compounds in vitro.

Comparison of four definitions of the metabolic syndrome in a Greek (Mediterranean) population.

BACKGROUND: There is a need to evaluate the prevalence of metabolic syndrome (MetS) diagnosed by the new Joint Interim Societies (JIS) MetS definition. The JIS definition was compared with three previous definitions to assess their ability to predict cardiovascular disease (CVD) risk. METHODS: A cross-sectional analysis of a representative sample of Greek adults (n = 9669) was performed to estimate the prevalence of MetS and CVD using the JIS vs. the three older definitions of MetS: the National Cholesterol Education Program-Adult Treatment Panel-III (NCEP-ATP-III), the International Diabetes Federation (IDF) and the American Heart Association/National Heart Lung and Blood Institute (AHA/NHLBI) definitions. RESULTS: The age-adjusted MetS prevalence was 45.7%, 43.4%, 24.5% and 26.3% (ANOVA p < 0.001) with the JIS, IDF, NCEP and AHA/NHLBI definitions. The prevalence of CVD was 11.4% in the whole study population and 17.6%, 18.3%, 23.3%, 22.6% and in subjects with MetS according to the JIS, IDF, NCEP and AHA/NHLBI definitions (ANOVA p < 0.001). The prevalence of CVD was only 10.4% (i.e., lower than in the whole study population) in subjects with MetS according to the JIS but not according to the NCEP-ATP-III and AHA/NHLBI definitions (p < 0.001 vs. subjects with MetS as defined by NCEP-ATP-III or AHA/NHLBI). CONCLUSIONS: When diagnosed according to the new JIS definition, the prevalence of MetS was high in a Greek Mediterranean cohort (nearly half of the adult population). The NCEP-ATP-III and AHA/NHLBI definitions were more predictive of CVD risk than the new JIS definition. These findings, though limited by the cross sectional analysis, may have implications regarding the choice of the definition to diagnose MetS.

Cytogenetic and antineoplastic effects of modified steroidal alkylators.

INTRODUCTION: The aim of this study was to design new potentially antineoplastic agents by combining nitrogen mustard with steroidal skeleton, in an effort to improve specificity and simultaneously to reduce systemic toxicity. The steroidal part is aimed to act as a biological platform enabling the alkylating moiety to approach its site of action by altering its physicochemical properties. MATERIALS AND METHODS: The compounds tested have, as alkylating agents, either p-N,N-bis(2-chloroethyl)aminophenyl-butyrate or p-N,N-bis(2-chloroethyl)aminophenyl-acetate esterified with a modified steroidal nucleus. The four newly synthesized compounds were compared on a molar basis, regarding their ability to induce sister chromatid exchanges and modify proliferation rate indices in cultured human lymphocytes. Life span of BDF1 mice inoculated with L1210 leukemia was also estimated (antileukemic activity). RESULTS: A compound having p-N,N-bis(2-chloroethyl)aminophenyl-acetate as the alkylator and two ketone groups in the steroidal part demonstrated the highest statistically significant enhancement of sister chromatid exchanges and suppression of proliferation rate indices, and also caused significant antineoplastic activity. The other compounds proved less active. CONCLUSION: These results suggest that cytogenetic and antileukemic activity of alkylating steroidal esters depends on the configuration of the whole molecule and the appropriate combination of the alkylator with the steroidal molecule.

Anticancer activity and quantitative-structure activity relationship (QSAR) studies of a series of antioxidant/anti-inflammatory aryl-acetic and hydroxamic acids.

A series of aryl-acetic acids and hydroxamic acids possessing antioxidant/anti-inflammatory activities were tested for anticancer activity using different cancer cell lines. The compounds have low antitumor activity considering the 1/IC(50) values attained for the cell lines. Compound 5iv presents the best anticancer activity. Moreover, they depict the same activity pattern, suggesting similar mechanisms of action correlated to their antioxidant activities. The obtained results subjected in a QSAR analysis. It seems reasonable to conclude that the same molecular structural features are responsible for the compounds biological activity, these being the electron accepting/donating ability and the molar volume. For all cellular lines (HT-29, A-549 and OAW-42) log 1/IC(50) exhibits a reasonable correlation with a two parameters relationship in which the Esp-min and D term are present. Apart from Esp-min the other descriptor found important for anticancer activity is the molar volume (MgVol). The QSAR analyses did not indicate any role for lipophilicity Electrostatic potential, dipole moment and the bulk, primarily affect the biological response.

Treatment outcomes of ligature-induced recession in the dog model using guided tissue regeneration or coronally positioned flap procedures.

AIM: The aims of the study were: (1) to determine the quality of the hard and soft tissues formed in segments treated with coronally positioned flaps alone (CPF group) or combined with a polylactic acid resorbable membrane (guided tissue regeneration--GTR group) in wide type defects (canine teeth), and (2) to evaluate the behaviour of the newly regenerated tissues to an experimentally induced inflammation initiated by microbial plaque at the submarginal level in recession type defects (premolar teeth). MATERIALS AND METHODS: The randomized block design was used in the study, with each dog receiving both treatments (GTR and CPF). Gingival recession defects were surgically created in the 2nd and 4th mandibular premolars and, after 10 weeks, also in the maxillary canines of three dogs. The defects in the premolar area were created earlier than the defects in the canine teeth so that both areas would be ready for biopsy at the same time. Two months after the creation of the defects the exposed roots in the control group of teeth were surgically covered with coronally positioned flaps only (CPF group), and in the test group of teeth a coronally positioned flap was used in combination with a resorbable membrane (GTR group). In the premolar teeth only, after a healing period of five months, cotton ligatures were placed intrasulcularly and these areas were left without plaque control for 10 weeks. Following this, biopsies were taken from the canines and the premolars in order to examine (1) the quality of the hard and soft tissues formed after five months of healing in the canine teeth and (2) the response of the newly formed tissues to microbial accumulation induced by the subgingival ligature placement. RESULTS: In the wide defects of the canine teeth, the use of the membrane produced a mean new attachment formation of 44%, while the repositioned flap technique produced 22% new attachment. The regeneration of bone was limited to the apical area for both techniques and amounted to 15% and 10%, respectively. In the narrow defects of the premolars both techniques produced comparable mean root coverage percentages. The inflammatory conditions created in the study led to a comparable loss of mean clinical attachment and an increase in tissue recession and the extent of the inflammatory process for both groups. CONCLUSIONS: The use of resorbable membranes for the treatment of wide recession type defects in the canine teeth (GTR group) produced significantly better clinical results, with higher mean root coverage and increased regenerative capacity of the periodontal tissues, compared with the coronally positioned flap technique (CPF group). Additionally, the regenerated tissues created after the use of both techniques in narrow recession defects (premolar teeth) demonstrated comparable resistance to the microbial accumulation conditions created.

Synthesis, in vivo antileukemic evaluation and comparative study of novel 5alpha-7-keto steroidal esters of chlorambucil and its active metabolite.

Recent structure-antileukemic activity studies showed that the steroidal part of complex molecules containing DNA alkylators does not play only the role of the "biological carrier". New such compounds designed to possess an allylic 7-ketone showed enhanced antileukemic potency compared with derivatives with a simple steroidal skeleton. In order to investigate whether the enhancement of the antileukemic potency is attributed to the introduction of the 7-ketone or to the Delta5-7-keto conjugated steroidal system we decided to reduce the Delta5 double bond. The 5alpha-7-keto-steroidal skeletons synthesized were tethered to chlorambucil and phenyl acetic acid's nitrogen mustard and studied against leukemia P338 in vivo. The reduction of the double bond had a negative impact on the antileukemic potency since the comparative study of the novel derivatives showed that a series of very potent Delta 5-7-keto-steroidal esters were converted by this modification to compounds with marginally accepted activity.

Effects of statin treatment in men and women with stable coronary heart disease: a subgroup analysis of the GREACE Study.

BACKGROUND: Reducing low-density lipoprotein cholesterol (LDL-C) levels to National Cholesterol Expert Panel (NCEP) goal is recommended. However, sex-specific effects may influence benefit. METHODS AND RESULTS: In this post hoc analysis of the GREek Atorvastatin and Coronary heart disease (CHD) Evaluation [GREACE] study we investigated the extent in vascular event reduction by statin treatment according to sex. From a total of 1600 patients with stable CHD, 624/176 and 632/168 were men/women on atorvastatin or on usual care, respectively. During 3-year follow-up, comparison of atorvastatin treatment with usual care demonstrated a relative risk reduction (RRR) of the primary end point (all vascular events) of 54% in women (hazard ratio [HR] 0.46, 95% confidence interval [CI] 0.24-0.87, p=0.003) and of 50% in men (HR 0.50, 95% CI 0.32-0.70, p<0.001). The fall in LDL-C levels played the key role in end point reduction in both sexes. However, in men there was an additional benefit related to the atorvastatin-induced increase in high density lipoprotein cholesterol (HDL-C) and estimated glomerular filtration rate (eGFR), while in women end points were related to a substantial triglycerides (TG) reduction. CONCLUSIONS: Treatment with atorvastatin to the NCEP LDL-C goal compared with 'usual care' significantly reduced CHD morbidity and mortality in both men and women. Both men and women benefited from statin treatment possibly with different mechanisms making a contribution over and above LDL-C reduction.

Spironolactone versus eplerenone for the treatment of idiopathic hyperaldosteronism.

The aim of this prospective, randomised, open-label, blinded-end point study was to compare the efficacy and safety of eplerenone versus spironolactone in patients with bilateral idiopathic hyperaldosteronism (IHA). After a 2-week washout period, 34 patients with IHA were assigned to receive either spironolactone 25 mg b.i.d. (n = 17) or eplerenone 25 mg b.i.d. (n = 17) for 24 weeks. If the patients' blood pressure (BP) was not < 140/90 mmHg, the doses were gradually increased up to 400 mg for spironolactone and 200 mg for eplerenone. If the patients' BP remained uncontrolled, a daily dose of hydrochlorothiazide 12.5 mg was added at week 16. The primary outcome was the percentage of patients with BP < 140/90 mmHg at 16 weeks (i.e., with aldosterone antagonist monotherapy). The patients' BP was normalised in 13 out of 17 (76.5%) and 14 out of 17 (82.4%) patients in the spironolactone and eplerenone groups, respectively (p = 1.00). Systolic BP decreased more rapidly with eplerenone. Serum potassium levels were normalised (> 3.5 mmol/l) in all patients at 4 weeks. Mild hyperkalaemia was observed in two patients receiving 400 mg of spironolactone and in three patients receiving 150 mg of eplerenone. Two patients presented with bilateral painful gynaecomastia at the end of week 16 while receiving 400 mg of spironolactone. Switching spironolactone to 150 mg of eplerenone daily resulted in resolution of gynaecomastia and also maintained BP control. At the end of the study, 19 patients were on eplerenone and 15 were on spironolactone. However, this did not affect the primary end point, because the switch from spironolactone to eplerenone (in two patients) occurred at the end of week 16. It was concluded that eplerenone was as effective as spironolactone in reducing BP in patients with IHA. The risk of mild hyperkalaemia was similar with both drugs.

Rational design, synthesis, and in vivo evaluation of the antileukemic activity of six new alkylating steroidal esters.

The synthesis and the in vivo evaluation against leukemias P388 and L1210 of six new alkylating steroidal esters are described. The esteric derivatives incorporating the 17beta-acetamido-B-lactamic steroidal skeleton exhibited increased antileukemic activity and lower toxicity, compared to the 17beta-acetamido-7-keto analogs. Among the 17beta-acetamido-B-lactamic steroidal esters, the most potent compound afforded four out of six cures in leukemia P388 and was measured to be almost non-toxic, producing significant low levels of toxicity.

Atorvastatin decreases triacylglycerol-associated risk of vascular events in coronary heart disease patients.

High triacylglycerol (TAG) levels may predict vascular risk. The effect of a statin-induced reduction in TAG levels, irrespective of HDL-C increase, on clinical outcome has not yet been addressed by an endpoint study in patients with coronary heart disease (CHD). The GREACE study compared usual with structured care aimed at achieving LDL-C = 100 mg/dL (2.6 mmol/L) by dose titration with atorvastatin. All patients had CHD and were followed for 3 years. This post hoc analysis of GREACE examines the effect of statins on TAG levels and their relation with cardiovascular disease (CVD) events in all patients and in the subgroup of patients with metabolic syndrome (MetS). Baseline TAG levels >150 mg/dL (1.7 mmol/L) were predictive of subsequent CVD events [cardiac mortality, non-fatal myocardial infarction (MI), unstable angina (UA), revascularisation, congestive heart failure (CHF), and stroke] only in statin untreated patients. Stepwise regression analysis showed that with every 20% statin-related TAG reduction there was a decrease in CVD risk by 12% (HR 0.88, 95% CI 0.75-0.95, P = 0.007) in the structured care group vs. the usual care group, by 8% (HR 0.92, 95% CI 0.81-0.97, P = 0.02) in all statin treated patients vs. the untreated ones and by 15% (HR 0.85, 95% CI 0.65-0.94, P = 0.005) in those with MetS treated with a statin vs. those untreated. Using the same analysis but only taking into consideration vascular events (cardiac mortality, non-fatal MI, UA, revascularisation, and stroke) there was a 18% (HR = 0.82, 95% CI 0.57-0.96, P = 0.03) decrease in risk in the MetS (+) patients treated with a statin vs. those not on a statin, and a decrease in risk by 16% (HR = 0.84, 95% CI 0.53-1.07, P = 0.08), when only hard vascular endpoints (cardiac mortality, non-fatal MI, and stroke) were considered. TAG levels are predictive of subsequent CVD events in statin untreated CHD patients. Statin (mainly atorvastatin)-induced decrease in TAG levels was related to a significant reduction in subsequent CVD events. This benefit was more pronounced in CHD MetS (+) patients.

Structure-antileukemic activity relationship study of B- and D-ring modified and nonmodified steroidal esters of 4-methyl-3-N,N-bis(2-chloroethyl)amino benzoic acid: a comparative study.

This study was designed as a rational continuation of our research regarding the functional requirements essential for the antileukemic activity of compounds comprising an alkylating moiety and a modified steroid. The steroidal esteric derivatives of 4-methyl-3-N,N-bis(2-chloroethyl)amino benzoic acid were tested on leukemias P388 and L1210 in vivo and in normal human lymphocytes in vitro. Among them the B-lactamic steroidal esters proved more potent antileukemic agents than the 7-oxidized and those with a simple B-ring, but not more effective inducers of DNA damage and cell cycle arrest in vitro. We speculate that these results indicate a different mechanism of action induced by the lactamized B steroidal ring, in comparison to the 7-keto or the D-lactamic groups, which involves the interaction of the -NHCO- moiety with cellularcomponents essential for tumor growth. 4-Methyl-3-N,N-bis(2-chloroethyl)amino benzoic acid proved a more proper module for the B-lactams than chlorambucil and phenyl acetic acid's nitrogen mustard probably because the esteric bond is less cleaved by the esterases, resulting in an increased concentration of the drug in the vinicity of the target site essential for an antineoplasmatic response.