Novel Coumarin-Steroid/Terpenoid Hybrids: In Vitro and In Silico Anticancer Studies.

We have synthesized a series of novel coumarin-steroid and triterpenoid hybrids and evaluated their potential anticancer activity through molecular docking calculations and in vitro antiproliferative assays. These hybrids, derived from estrone and oleanolic acid, were linked via hydrocarbon spacers of varying lengths. Molecular docking studies against human aromatase revealed strong interactions, particularly for compound 11d, which exhibited significant binding affinity (-12.6308 kcal/mol). In vitro assays demonstrated that compounds 6b and 11d had notable antiproliferative effects, with GI50 values of 5.4 and 7.0 µM against WiDr (colon) and HeLa (cervix) cancer cells, respectively. These findings highlight the potential of these hybrids as novel anticancer agents targeting aromatase, warranting further investigation and optimization.

Enhancing Giardicidal Activity and Aqueous Solubility through the Development of "RetroABZ", a Regioisomer of Albendazole: In Vitro, In Vivo, and In Silico Studies.

Parasitic diseases, including giardiasis caused by Giardia lamblia (G. lamblia), present a considerable global health burden. The limited effectiveness and adverse effects of current treatment options underscore the necessity for novel therapeutic compounds. In this study, we employed a rational design strategy to synthesize retroalbendazole (RetroABZ), aiming to address the limitations associated with albendazole, a commonly used drug for giardiasis treatment. RetroABZ exhibited enhanced in vitro activity against G. lamblia trophozoites, demonstrating nanomolar potency (IC50 = 83 nM), outperforming albendazole (189 nM). Moreover, our in vivo murine model of giardiasis displayed a strong correlation, supporting the efficacy of RetroABZ, which exhibited an eleven-fold increase in potency compared to albendazole, with median effective dose (ED50) values of 5 µg/kg and 55 µg/kg, respectively. A notable finding was RetroABZ's significantly improved water solubility (245.74 µg/mL), representing a 23-fold increase compared to albendazole, thereby offering potential opportunities for developing derivatives that effectively target invasive parasites. The molecular docking study revealed that RetroABZ displays an interaction profile with tubulin similar to albendazole, forming hydrogen bonds with Glu198 and Cys236 of the ß-tubulin. Additionally, molecular dynamics studies demonstrated that RetroABZ has a greater number of hydrophobic interactions with the binding site in the ß-tubulin, due to the orientation of the propylthio substituent. Consequently, RetroABZ exhibited a higher affinity compared to albendazole. Overall, our findings underscore RetroABZ's potential as a promising therapeutic candidate not only for giardiasis but also for other parasitic diseases.

Design, Synthesis, and In Silico Multitarget Pharmacological Simulations of Acid Bioisosteres with a Validated In Vivo Antihyperglycemic Effect.

Substituted phenylacetic (1-3), phenylpropanoic (4-6), and benzylidenethiazolidine-2,4-dione (7-9) derivatives were designed according to a multitarget unified pharmacophore pattern that has shown robust antidiabetic activity. This bioactivity is due to the simultaneous polypharmacological stimulation of receptors PPARα, PPARγ, and GPR40 and the enzyme inhibition of aldose reductase (AR) and protein tyrosine phosphatase 1B (PTP-1B). The nine compounds share the same four pharmacophore elements: an acid moiety, an aromatic ring, a bulky hydrophobic group, and a flexible linker between the latter two elements. Addition and substitution reactions were performed to obtain molecules at moderated yields. In silico pharmacological consensus analysis (PHACA) was conducted to determine their possible modes of action, protein affinities, toxicological activities, and drug-like properties. The results were combined with in vivo assays to evaluate the ability of these compounds to decrease glucose levels in diabetic mice at a 100 mg/kg single dose. Compounds 6 (a phenylpropanoic acid derivative) and 9 (a benzylidenethiazolidine-2,4-dione derivative) ameliorated the hyperglycemic peak in a statically significant manner in a mouse model of type 2 diabetes. Finally, molecular dynamics simulations were executed on the top performing compounds to shed light on their mechanism of action. The simulations showed the flexible nature of the binding pocket of AR, and showed that both compounds remained bound during the simulation time, although not sharing the same binding mode. In conclusion, we designed nine acid bioisosteres with robust in vivo antihyperglycemic activity that were predicted to have favorable pharmacokinetic and toxicological profiles. Together, these findings provide evidence that supports the molecular design we employed, where the unified pharmacophores possess a strong antidiabetic action due to their multitarget activation.

Metronidazole and Secnidazole Carbamates: Synthesis, Antiprotozoal Activity, and Molecular Dynamics Studies.

We prepared a series of 10 carbamates derivatives based on two common antiprotozoal drugs: metronidazole (1-5) and secnidazole (6-10). The compounds were tested in vitro against a set of two amitochondriate protozoa: Giardia duodenalis and Trichomonas vaginalis. Compounds 1-10 showed strong antiprotozoal activities, with potency values in the low micromolar-to-nanomolar range, being more active than their parent drugs. Metronidazole carbamate (1) was the most active of the series, with nanomolar activities against G. duodenalis (IC50 = 460 nM) and T. vaginalis (IC50 = 60 nM). The potency of compound 1 was 10 times greater than that of metronidazole against both parasites. None of compounds showed in vitro cytotoxicity against VERO cells tested at 100 µM. Molecular dynamics of compounds 1-10, secnidazole, and metronidazole onto the ligand binding site of pyruvate-ferredoxin oxidoreductase of T. vaginalis and the modeled -tubulin of G. duodenalis revealed putative molecular interactions with key residues in the binding site of both proteins implicated in the mode of action of the parent drugs.

Design, Synthesis and in Combo Antidiabetic Bioevaluation of Multitarget Phenylpropanoic Acids.

We have synthesized a small series of five 3-[4-arylmethoxy)phenyl]propanoic acids employing an easy and short synthetic pathway. The compounds were tested in vitro against a set of four protein targets identified as key elements in diabetes: G protein-coupled receptor 40 (GPR40), aldose reductase (AKR1B1), peroxisome proliferator-activated receptor gama (PPARγ) and solute carrier family 2 (facilitated glucose transporter), member 4 (GLUT-4). Compound 1 displayed an EC50 value of 0.075 µM against GPR40 and was an AKR1B1 inhibitor, showing IC50 = 7.4 µM. Compounds 2 and 3 act as slightly AKR1B1 inhibitors, potent GPR40 agonists and showed an increase of 2 to 4-times in the mRNA expression of PPARγ, as well as the GLUT-4 levels. Docking studies were conducted in order to explain the polypharmacological mode of action and the interaction binding mode of the most active molecules on these targets, showing several coincidences with co-crystal ligands. Compounds 1-3 were tested in vivo at an explorative 100 mg/kg dose, being 2 and 3 orally actives, reducing glucose levels in a non-insulin-dependent diabetes mice model. Compounds 2 and 3 displayed robust in vitro potency and in vivo efficacy, and could be considered as promising multitarget antidiabetic candidates. This is the first report of a single molecule with these four polypharmacological target action.

Proton pump inhibitors drastically modify triosephosphate isomerase from Giardia lamblia at functional and structural levels, providing molecular leads in the design of new antigiardiasic drugs.

BACKGROUND: Proton pump inhibitors (PPIs) are extensively used in clinical practice because of their effectiveness and safety. Omeprazole is one of the best-selling drugs worldwide and, with other PPIs, has been proposed to be potential drugs for the treatment of several diseases. We demonstrated that omeprazole shows cytotoxic effects in Giardia and concomitantly inactivates giardial triosephosphate isomerase (GlTIM). Therefore, we evaluated the efficiency of commercially available PPIs to inactivate this enzyme. METHODS: We assayed the effect of PPIs on the GlTIM WT, single Cys mutants, and the human counterpart, following enzyme activity, thermal stability, exposure of hydrophobic regions, and susceptibility to limited proteolysis. RESULTS: PPIs efficiently inactivated GlTIM; however, rabeprazole was the best inactivating drug and was nearly ten times more effective. The mechanism of inactivation by PPIs was through the modification of the Cys 222 residue. Moreover, there are important changes at the structural level, the thermal stability of inactivated-GlTIM was drastically diminished and the structural rigidity was lost, as observed by the exposure of hydrophobic regions and their susceptibility to limited proteolysis. CONCLUSIONS: Our results demonstrate that rabeprazole is the most potent PPI for GlTIM inactivation and that all PPIs tested have substantial abilities to alter GITIM at the structural level, causing serious damage. GENERAL SIGNIFICANCE: This is the first report demonstrating the effectiveness of commercial PPIs on a glycolytic parasitic enzyme, with structural features well known. This study is a step forward in the use and understanding the implicated mechanisms of new antigiardiasic drugs safe in humans.

Synthesis, in vitro and in vivo giardicidal activity of nitrothiazole-NSAID chimeras displaying broad antiprotozoal spectrum.

We designed and synthesized five new 5-nitrothiazole-NSAID chimeras as analogues of nitazoxanide, using a DCC-activated amidation. Compounds 1-5 were tested in vitro against a panel of five protozoa: 2 amitochondriates (Giardia intestinalis, Trichomonas vaginalis) and 3 kinetoplastids (Leishmania mexicana, Leishmania amazonensis and Trypanosoma cruzi). All chimeras showed broad spectrum and potent antiprotozoal activities, with IC50 values ranging from the low micromolar to nanomolar order. Compounds 1-5 were even more active than metronidazole and nitazoxanide, two marketed first-line drugs against giardiasis. In particular, compound 4 (an indomethacin hybrid) was one of the most potent of the series, inhibiting G. intestinalis growth in vitro with an IC50 of 0.145µM. Compound 4 was 38-times more potent than metronidazole and 8-times more active than nitazoxanide. The in vivo giardicidal effect of 4 was evaluated in a CD-1 mouse model obtaining a median effective dose of 1.709µg/kg (3.53nmol/kg), a 321-fold and 1015-fold increase in effectiveness after intragastric administration over metronidazole and nitazoxanide, respectively. Compounds 1 and 3 (hybrids of ibuprofen and clofibric acid), showed potent giardicidal activities in the in vitro as well as in the in vivo assays after oral administration. Therefore, compounds 1-5 constitute promising drug candidates for further testing in experimental chemotherapy against giardiasis, trichomoniasis, leishmaniasis and even trypanosomiasis infections.

Synthesis of nitro(benzo)thiazole acetamides and in vitro antiprotozoal effect against amitochondriate parasites Giardia intestinalis and Trichomonas vaginalis.

We synthesized four 5-nitrothiazole (1-4) and four 6-nitrobenzothiazole acetamides (5-8) using an easy two step synthetic route. All compounds were tested in vitro against amitochondriate parasites Giardia intestinalis and Trichomonas vaginalis, showing excellent antiprotozoal effects. IC50's of the most potent compounds range from nanomolar to low micromolar order, being more active than their drugs of choice. Compound 1 (IC50=122 nM), was 44-times more active than Metronidazole, and 10-fold more effective than Nitazoxanide against G. intestinalis and showed good trichomonicidal activity (IC50=2.24 µM). This compound did not display in vitro cytotoxicity against VERO cells. The in vitro inhibitory effect of compounds 1-8 and Nitazoxanide against G. intestinalis fructose-1,6-biphosphate aldolase (GiFBPA) was evaluated as potential drug target, showing a clear inhibitory effect over the enzyme activity. Molecular docking of compounds 1, 4 and Nitazoxanide into the ligand binding pocket of GiFBPA, revealed contacts with the active site residues of the enzyme. Ligand efficiency metrics of 1 revealed optimal combinations of physicochemical and antiprotozoal properties, better than Nitazoxanide.

Vitamins, fatty acids, and antioxidant capacity stability during storage of freeze-dried human milk.

Although freezing is the most common method used to preserve human milk, nutritional and immunological components may be lost during storage. Freeze-drying could increase the shelf life of human milk, while preserving its original characteristics. Seventy-two samples of freeze-dried human milk were stored for different periods of time, up to a maximum of 3 months, at 4 °C or 40 °C. Vitamin C, tocopherols, antioxidant capacity, and fatty acids composition were analyzed. A new HILIC-UHPLC method improving vitamin C determination was also validated. Ascorbic acid and total vitamin C concentrations significantly decreased at both temperatures, while antioxidant capacity only decreased at 40 °C. Fatty acids composition and both γ-tocopherol and δ-tocopherol contents remained unaltered. The stability after storage of freeze-dried milk was higher than that reported for frozen or fresh milk indicating that freeze-drying is a promising option to improve the preservation of human milk in banks.

2-(4-Acetamido-phen-oxy)-2-methyl-propanoic acid.

In the title compound, C12H15NO4, the dihedral angle between the acetamide group and the ring is 29.6 (2)(su?)°. In the crystal mol-ecules are linked through N-H⋯O and O-H⋯O hydrogen bonds, thereby forming corrugated sheets propagating in the ac plane. These sheets are composed of R4(4)(28) graph-set motifs.

Enantioselective Suzuki cross-coupling of 1,2-diboryl cyclopropanes.

Herein, we describe the catalytic enantioselective cross-coupling of 1,2-bisboronic esters. Prior work on group specific cross coupling is limited to the use of geminal bis-boronates. This desymmetrization provides a novel approach to prepare enantioenriched cyclopropyl boronates with three contiguous stereocenters, that could be further derivatized through selective functionalization of the carbon-boron bond. Our results suggest that transmetallation, which is the enantiodetermining step, takes place with retention of stereochemistry at carbon.

Synthesis, antiproliferative evaluation and in silico studies of a novel steroidal spiro morpholinone.

Estrogens play a pivotal role in the development of estrogen-dependent breast cancer and other hormone-dependent disorders. A common strategy to overcome the pathological effects of estrogens is the use of aromatase inhibitors (AIs), which bind to the enzyme and prevent the union with the natural substrate, decreasing the amount of estrogens produced. Several AIs have been developed, including inhibitors with a steroidal backbone and a nitrogen heterocycle in their structure. Encouraged by the notable results presented by current and clinical steroidal drugs, herein we present the synthesis of a steroidal spiro morpholinone derivative as a plausible aromatase inhibitor. The morpholinone derivative was synthesized over a six-step methodology starting from estrone. The title compound and its hydroxychloroacetamide derivative precursor were evaluated for their antiproliferative profile against estrogen-dependent and independent solid tumor cell lines: A549, HBL-100, HeLa, SW1573, T-47D and WiDr. Both compounds exhibited a potent antiproliferative activity in the micromolar range against the six cancer cell lines, with the hydroxychloroacetamide derivative precursor being a more potent inhibitor (GI50 = 0.25-2.4 µM) than the morpholinone derivative (GI50 = 2.0-11 µM). Furthermore, both compounds showed, in almost all cases, better GI50 values than the steroidal anticancer drugs abiraterone and galeterone. Docking simulations of the derivatives were performed in order to explain the experimental biological activity. The results showed interactions with the iron heme (derivative 3) and important residues of the steroidal binding-site (Met374) for the inhibition of human aromatase. A correlation was found between in vitro assays and the score obtained from the molecular docking study.

Synthesis, In Vitro, In Vivo and In Silico Antidiabetic Bioassays of 4-Nitro(thio)phenoxyisobutyric Acids Acting as Unexpected PPARγ Modulators: An In Combo Study.

Four isobutyric acids (two nitro and two acetamido derivatives) were prepared in two steps and characterized using spectral analysis. The mRNA concentrations of PPARγ and GLUT-4 (two proteins documented as key diabetes targets) were increased by 3T3-L1 adipocytes treated with compounds 1-4, but an absence of in vitro expression of PPARα was observed. Docking and molecular dynamics studies revealed the plausible interaction between the synthesized compounds and PPARγ. In vivo studies established that compounds 1-4 have antihyperglycemic modes of action associated with insulin sensitization. Nitrocompound 2 was the most promising of the series, being orally active, and one of multiple modes of action could be selective PPARγ modulation due to its extra anchoring with Gln-286. In conclusion, we demonstrated that nitrocompound 2 showed strong in vitro and in vivo effects and can be considered as an experimental antidiabetic candidate.

Assessment of diagnostic capacity and decision-making based on the 2015 American Thyroid Association ultrasound classification system.

BACKGROUND: This study evaluates the American Thyroid Association (ATA) ultrasound (US) classification system for the initial assessment of thyroid nodules to determine if it indeed facilitates clinical decision-making. AIM: To perform a systematic review and meta-analysis of the diagnostic value of the ATA US classification system for the initial assessment of thyroid nodules. METHODS: In accordance with the PRISMA statement for diagnostic test accuracy, we selected articles that evaluated the 2015 ATA US pattern guidelines using a diagnostic gold standard. We analyzed these cases using traditional diagnostic parameters, as well as the threshold approach to clinical decision-making and decision curve analysis. RESULTS: We reviewed 13 articles with 8445 thyroid nodules, which were classified according to 2015 ATA patterns. Of these, 46.62% were malignant. No cancer was found in any of the ATA benign pattern nodules. The Bayesian analysis post-test probability for cancer in each classification was: (1) Very-low suspicion, 0.85%; (2) Low, 2.6%; (3) Intermediate, 6.7%; and (4) High, 40.9%. The net benefit (NB), expressed as avoided interventions, indicated that the highest capacity to avoid unnecessary fine needle aspiration biopsy (FNAB) in the patterns that we studied was 42, 31, 35, and 43 of every 100 FNABs. The NB calculation for a probability threshold of 11% for each of the ATA suspicion patterns studied is less than that of performing FNAB on all nodules. CONCLUSION: These three types of analysis have shown that only the ATA high-suspicion diagnostic pattern is clinically useful, in which case, FNAB should be performed. However, the curve decision analysis has demonstrated that using the ATA US risk patterns to decide which patients need FNAB does not provide a greater benefit than performing FNAB on all thyroid nodules. Therefore, it is likely that a better way to approach the assessment of thyroid nodules would be to perform FNAB on all non-cystic nodules, as the present analysis has shown the ATA risk patterns do not provide an adequate clinical decision-making framework.

Antidiabetic effect of Cordia morelosana, chemical and pharmacological studies.

ETHNOPHARMACOLOGICAL IMPORTANCE: CORDIA MORELOSANA: Standley (Boraginaceae) is commonly used in folk medicine for the treatment of diarrhoea, kidney inflammation, diabetes, lung pain, bronchitis, asthma, hoarseness, cough and fever. AIM: Current work was conducted to develop a bio-guided isolation of antidiabetic compounds from ethanolic extract of Cordia morelosana (EECm). MATERIAL AND METHODS: The phytochemical bio-guided study was conducted by successive chromatographic techniques, and isolated compounds were characterized by 1D and 2D-NMR experiments. The in vivo antihyperglycemic and antidiabetic activities of EECm (100 mg/kg), and methyl rosmarinate (MR, 50 mg/kg) were determined on normoglycemic and diabetic murine models. Additionally, the in vitro activity was conducted to determine α-glucosidase inhibitory effect, and PPARs, GLUT4 and FATP expression on 3T3-L1 cells by RT-PCR. Acute and sub-chronic toxicological studies for EECm were conducted on rats, following the OECD guidelines (No. 420 and 407). RESULTS: EECm promotes significant α-glucosidase inhibition (55.6%) at 1 mg/kg respect to the control. Also, EECm (100 mg/kg) showed significant antihyperglycemic effect on oral glucose tolerance test (OGTT), and in non-insulin dependent type 2 diabetes (NIDD) model, had antidiabetic activity (p < 0.001) compared to controls. The bio-guided isolation allowed to obtain four known compounds described as rosmarinic acid (RA), methyl rosmarinate (MR), nicotiflorine and 1-O-methyl-scyllo-inositol. On the other hand, MR showed significant antidiabetic and anthiyperglycemic activities (p < 0.05), and overexpression of PPARγ, PPARα, GLUT-4 and FATP than control. Docking studies were conducted with PPARγ and PPARα, showing interesting binding mode profile on those targets. Finally, EECm displayed a LD50 > 2000 mg/kg and sub-chronic toxicological study reveals no toxic signs in animals tested compared to control. CONCLUSION: EECm showed significant antihyperglycemic and antidiabetic actions being RA and MR the main antidiabetic metabolites.

Intraoperative care for aortic surgery using circulatory arrest.

The total circulatory arrest (CA) is necessary to achieve optimal surgical conditions in certain aortic pathologies, especially in those affecting the ascending aorta and aortic arch. During this procedure it is necessary to protect all the organs of ischemia, especially those of the central nervous system and for this purpose several strategies have been developed. The first and most important protective method is systemic hypothermia. The degree of hypothermia and the route of application have been evolving and currently tend to use moderate hypothermia (MH) (20.1-28 °C) associated with unilateral or bilateral selective cerebral perfusion methods. In this way the neurological results are better, the interval of security is greater and the times of extracorporeal circulation are smaller. Even so, it is necessary to take into account that there is the possibility of ischemia in the lower part of the body, especially of the abdominal viscera and the spinal cord, therefore the time of circulatory stop should be limited and not to exceed 80 minutes. Evidence of possible neurological drug protection is very weak and only mannitol, magnesium, and statins can produce some benefit. Inhalational anesthetics and some intravenous seem to have advantages, but more studies would be needed to test their long-term benefit. Other important parameters to be monitored during these procedures are blood glucose, anemia and coagulation disorders and acid-base balance. The recommended monitoring is common in complex cardiovascular procedures and it is of special importance the neurological monitoring that can be performed with several techniques, although currently the most used are Bispectral Index (BIS) and Near-Infrared Spectroscopy (NIRS). It is also essential to monitor the temperature routinely at the nasopharyngeal and bladder level and it is important to control coagulation with rotational thromboelastometry (ROTEM).

[Dyspareunia after total abdominal hysterectomy. Anatomical relation]. / Dispareunia post-histerectomía total abdominal. Relación anatómica.

BACKGROUND: We undertook this study to determine whether anatomic changes after total abdominal hysterectomy are a cause of dyspareunia in premenopausal women. METHODS: This is a comparative, prospective and longitudinal study in 50 premenopausal women with benign uterine disease without dyspareunia treated with total abdominal hysterectomy. Primary variable was presence of postsurgical dyspareunia. Secondary variables are presurgical and assessment 3 months after surgery of left, right, anterior and posterior vaginal longitude (VLL, VRL, VAL and VPL, respectively) expressed in centimeters, as well as of the vaginal volume (VV). Statistical analysis for mean, central tendency and t-test. Group 1 (G1) is comprised of patients with postsurgical dyspareunia and Group 2 (G2) is comprised of patients without dyspareunia. RESULTS: In G1, three patients (mean age: 42 years) had dyspareunia, pre- and postsurgical mean values were VV 146.6 and 100, VLL 8 and 7.3, VPL 9.16 and 7.3, VLL 8 and 7.3, VRL 8 and 7.3. In G2, 47 patients (mean age: 40.36 years) were without dyspareunia, pre- and postsurgical values were VV 150.6 and 121.57, VLL 8.81 and 8.12, VPL 9.7 and 8.69, VLL 9.24 and 8.3, VRL 9.28 and 8.33. We did not find significant differences between the groups. Two of the three patients with dyspareunia had a vaginal granuloma, but the third case did not show an anatomical cause. CONCLUSIONS: There is no relationship between total abdominal hysterectomy in premenopausal women and anatomical vaginal changes after surgery as assessed by vaginal volume and longitude. Presence of vaginal granuloma was responsible for dyspareunia in 4% of cases. Dyspareunia was found in 2% of premenopausal women without posthysterectomy anatomical cause.

TSH alone is not sufficient to exclude all patients with a functioning thyroid nodule from undergoing testing to exclude thyroid cancer.

PURPOSE: The purpose of the study was to analyze whether the thyroid-stimulating hormone (TSH) alone avoids tests to exclude malignancy in all patients with functional thyroid nodules (FTN). METHODS: Sixty-nine patients with FTN on (99m)Tc scintigraphy, radioiodine uptake test (RIU), (99m)Tc thyroid uptake, TSH assay, T3, and T4 obtained within 48 h were retrospectively identified out of 2,356 thyroid scans performed from January 2000 to April 2007. FTNs were classified as causing total, partial, or no inhibition of the thyroid as group 1, 2, or 3, respectively. RESULTS: TSH was subnormal in 21 of 69 (30.43%) patients. In group 1 (N = 23, 33.3%), TSH was subnormal, normal, and high in eight, nine, and six patients; in group 2 (N = 17, 24.6%), TSH was subnormal, normal, and high in four, six, and seven patients, and in group 3 (N = 29, 42%), TSH was subnormal, normal, and high in 9, 13, and 7 patients, respectively. TSH was significantly lower in group 1. In T3, T4, (99m)Tc thyroid uptake, and RIU, there were no differences between the three groups. CONCLUSIONS: Only 30.43% of patients had subnormal TSH. TSH alone cannot avoid tests to exclude malignancy in all patients with FTN. FTN existence can only be accurately assessed by thyroid scintigraphy. The current incidence of FTN may be unknown because scintigraphy is not routinely performed in all patients with thyroid nodules. Thyroid scintigraphy of patients with high TSH can detect diseases such as Hashimoto's thyroiditis and identify patients with FTN in whom no further diagnostic procedures would be needed in patients with normal TSH levels with nondiagnostic fine-needle aspiration results.

Dispareunia post-histerectomía total abdominal: relación anatómica / Dyspareunia after total abdominal hysterectomy: anatomical relation

Objetivo: conocer si los cambios anatómicos poshisterectomía total abdominal producen dispareunia en pacientes premenopáusicas. Material y métodos: estudio comparativo, prospectivo, longitudinal, de 50 pacientes premenopáusicas sometidas a histerectomía total abdominal por enfermedad uterina benigna sin dispareunia prequirúrgica. Se realizaron valoraciones pre y posperatorias del volumen vaginal y de las longitudes vaginales izquierda, derecha, anterior y posterior. El análisis estadístico se llevó a cabo por medidas de tendencia central y prueba t, agrupando a las pacientes en dos grupos: con dispareunia posoperatoria (grupo I) y sin dispareunia posoperatoria (grupo II). Resultados: grupo I, tres pacientes con los siguientes valores preoperatorios y posoperatorios: volumen vaginal de 146.6 y 100 cm3, longitud vaginal anterior de 8 y 7.3 cm, posterior de 9.16 y 7.3 cm, izquierda de 8 y 7.3 cm, y derecha de 8 y 7.3 cm. Grupo II, 47 pacientes con los siguientes valores preoperatorios y posoperatorios: volumen vaginal de 150.6 y 121.6 cm3, longitud vaginal anterior de 8.81 y 8.12 cm, posterior de 9.7 y 8.69 cm, izquierda de 9.24 y 8.3 cm, y derecha de 9.28 y 8.33 cm. Entre los grupos no encontramos diferencias estadísticamente significativas en volumen ni longitudes vaginales. En dos casos con dispareunia se encontró granuloma en cúpula vaginal que remitió con la resección; en otro no hubo implicación anatómica Conclusiones: no existió relación entre la dispareunia y los cambios de volumen y longitudes vaginales poshisterectomía. El granuloma en la cúpula vaginal fue responsable de 4 % de dispareunia. La dispareunia poshisterectomía total abdominal en paciente premenopáusicas sin causa anatómica aparente se presentó en 2 %.

BACKGROUND: We undertook this study to determine whether anatomic changes after total abdominal hysterectomy are a cause of dyspareunia in premenopausal women. METHODS: This is a comparative, prospective and longitudinal study in 50 premenopausal women with benign uterine disease without dyspareunia treated with total abdominal hysterectomy. Primary variable was presence of postsurgical dyspareunia. Secondary variables are presurgical and assessment 3 months after surgery of left, right, anterior and posterior vaginal longitude (VLL, VRL, VAL and VPL, respectively) expressed in centimeters, as well as of the vaginal volume (VV). Statistical analysis for mean, central tendency and t-test. Group 1 (G1) is comprised of patients with postsurgical dyspareunia and Group 2 (G2) is comprised of patients without dyspareunia. RESULTS: In G1, three patients (mean age: 42 years) had dyspareunia, pre- and postsurgical mean values were VV 146.6 and 100, VLL 8 and 7.3, VPL 9.16 and 7.3, VLL 8 and 7.3, VRL 8 and 7.3. In G2, 47 patients (mean age: 40.36 years) were without dyspareunia, pre- and postsurgical values were VV 150.6 and 121.57, VLL 8.81 and 8.12, VPL 9.7 and 8.69, VLL 9.24 and 8.3, VRL 9.28 and 8.33. We did not find significant differences between the groups. Two of the three patients with dyspareunia had a vaginal granuloma, but the third case did not show an anatomical cause. CONCLUSIONS: There is no relationship between total abdominal hysterectomy in premenopausal women and anatomical vaginal changes after surgery as assessed by vaginal volume and longitude. Presence of vaginal granuloma was responsible for dyspareunia in 4% of cases. Dyspareunia was found in 2% of premenopausal women without posthysterectomy anatomical cause.