TEDE Communidade:
https://tedebc.ufma.br/jspui/handle/tede/tede/544
2024-03-28T15:52:04ZEfeito antitumoral da moxidectina e seu potencial sinérgico à quimioterapia com cisplatina
https://tedebc.ufma.br/jspui/handle/tede/tede/5173
Título: Efeito antitumoral da moxidectina e seu potencial sinérgico à quimioterapia com cisplatina
Autor: BUTARELLI, Ana Luiza de Araújo
Primeiro orientador: SANTOS, Ana Paula Silva de Azevedo dos
Abstract: The repositioning of drugs as a therapeutic alternative for cancer has gained
prominence through the use of medicines approved in preclinical and clinical trials,
reducing expenses and the development time of new pharmaceuticals. In this
context, Moxidectin (MOX) is a broad-spectrum anthelmintic belonging to the
macrocyclic lactone family. Unlike other drugs in the same family, there is a lack of
studies exploring its therapeutic potential. Therefore, the aim of this study was to
evaluate the antitumor potential of MOX on cervical cancer cell lines (HeLa and
SiHa) and breast cancer cell lines (MCF-7 and MDA-MB-231). Cell viability was
assessed after 24 and 48 hours of MOX treatment (0.48 to 62 μM) using the MTT
reduction assay to determine the IC50 and selectivity index. Proliferative capacity was
evaluated in the colony formation assay, as well as the morphology of treated cells.
To assess the possible mechanism of action, cell death processes (apoptosis and
necrosis) and cell cycle were examined, including the effect of MOX in combination
with cisplatin. Results demonstrate that MOX selectively reduced cell viability in all
evaluated cell lines, except for HeLa. MDA-MB-231 and SiHa cell lines were more
sensitive to treatment, with IC50 values ranging from 1.055 to 4.030 μM, suggesting
time-dependent toxicity. Additionally, MOX significantly reduced the ability to form
new colonies in all treated cells. Data showed that MOX induced apoptosis in tumor
cells with a synergistic effect with cisplatin, increasing cell death by over 80%.
Combined treatment in the MCF-7 cell line resulted in an additive effect on apoptosis
induction and cell cycle arrest in the S phase (49.2% of cells), suggesting cell cycle
arrest as the pro-apoptotic pathway. These findings were supported by
morphological changes observed in treated cells, including condensed nuclei, loss of
cytoplasmic volume, and loss of cell adhesion. Conversely, in other cell lines, MOX
did not induce significant changes in the cell cycle. Overall, the data highlight the
antitumor activity of MOX, contributing to its repositioning in therapeutic regimens as
a pharmacological adjuvant in antitumor chemotherapy.
Instituição: Universidade Federal do Maranhão
Tipo do documento: Dissertação2024-01-18T00:00:00ZEstudo da ação antimicrobiana e imunomoduladora de produtos naturais associados
https://tedebc.ufma.br/jspui/handle/tede/tede/5158
Título: Estudo da ação antimicrobiana e imunomoduladora de produtos naturais associados
Autor: MENDES, Priscila Mendonça
Primeiro orientador: MACIEL, Márcia Cristina Gonçalves
Abstract: Cutaneous wound healing is a highly complex and dynamic mechanism aimed at restoring
damaged tissue. However, several factors can interfere with the normal repair of wound healing,
such as infections, which cause continuous and persistent inflammation, resulting in excessive
healing and the formation of fibroproliferative scars, including keloids and hypertrophic scars.
These conditions can lead to functional and aesthetic losses, making proper development of this
process crucial for maintaining skin function. The aim of this study was to review the literature
on the therapeutic potential of the Punica granatum species and to investigate the
immunomodulatory and antibacterial potential of a nanoemulsion containing the association of
natural products (PPG) on a murine model of wounds infected with methicillin-resistant
Staphyloccocus aureus (MRSA). Chapter I is entitled: "Therapeutic Potential of Punica
granatum and its Isolated Compounds: Evidence-Based Advances for Treating Bacterial
Infections" and Chapter II presents the experimental study of the treatment of infected wounds
using the formulation containing a combination of natural products. In the experimental study,
excisional wounds (78.5 mm2
) were induced on the back of female Swiss mice, the animals
were allocated to three groups (n=14), including negative control (CTRL); Fibrinase® (DFC,
positive control); a nanoemulsion containing the association of natural products (PPG). After
lesion induction, the infected groups received approximately 1.5×108 CFU/wound and were
treated daily from day 1 to day 10 post-infection. The diameter of the wound and the percentage
of healing were investigated using ImageJ software. Macroscopic analysis of the wounds was
carried out every other day. At random, animals from each group were euthanized on days 3, 7
and 10 and then the skin from the injured area was removed for analysis of histological
parameters (epithelialization, inflammatory cell infiltration (PMN), fibroblast proliferation,
collagen deposition and angiogenesis). The levels of inflammatory mediators (IL-2; IL4; IL-6;
IFN-γ; TNF- α; IL-17A; IL-10) were measured in the serum and the count of colony-forming
units (CFU) present in the wounds was analyzed to verify the antibacterial activity of PPG at
the three time points. Topical treatment of wounds in mice with infected lesions induced
complete wound retraction on day 10 in all groups. Topical application of PPG was able to
significantly (p < 0.05) increase macrophage proliferation (p=0.013; CTRL= 2.33±0.51;
DFC=.33±0.51; PPG=2.33±0.51) and reduce the PMN index (p=0.038; CTRL=2.33±0.51,
DFC=1.66±0.51; PPG=2.00±0.81) on the 7th day of treatment. In addition, it was able to
increase collagen deposition on day 10 (p=0.038; CTRL=2.33±0.51; DFC=2.33±0.51;
PPG=3.00±0.00) and angiogenesis (p=0.023; CTRL=1.50±0.57; DFC=2.00±0.00;
PPG=2.33±0.51). The positive effects of PPG treatment on reducing bacterial load on days 7
(CTRL=9.71±0.14; DFC=9.72±0.04; PPG=9.39±0.22 Log CFU/mL) and 10
(CTRL=10.67±0.09; DFC=10.18±0.11; PPG=10.31±0.22 Log UFC/mL) and increased IFN-γ
(p= 0.0373; CTRL=0.00±0.00; DFC=0.04±0.11; PPG=0.76±1.32). In conclusion, the
nanoemulsion proved to be a promising alternative for the treatment of infected wounds, not
only for its effect in controlling the infectious agent, but also for promoting effective tissue
repair. These events are directly related to the improvement in the appearance of the injured
area, highlighting the potential clinical application of PPG gel as a therapeutic approach for
infected wounds, with a positive impact on the quality and effectiveness of the healing process.
Instituição: Universidade Federal do Maranhão
Tipo do documento: Dissertação; Documento sob sigilo. Prazo provável para disponibilização total: 21/12/2024. Motivo do sigilo: patente2023-12-05T00:00:00ZAvaliação da atividade antimicrobiana dos compostos fitoquímicos da fração acetato de etila do extrato de folhas de urucum (Bixa Orellana) em modelo experimental de bexiga neurogênica
https://tedebc.ufma.br/jspui/handle/tede/tede/5113
Título: Avaliação da atividade antimicrobiana dos compostos fitoquímicos da fração acetato de etila do extrato de folhas de urucum (Bixa Orellana) em modelo experimental de bexiga neurogênica
Autor: COUTINHO, Gabrielle Guedes
Primeiro orientador: CARVALHO, Rafael Cardoso
Abstract: Neurogenic Bladder (BN) or lower urinary tract neurogenic dysfunction is a
medical and social problem resulting from abnormal neural communication
between the bladder and the nervous system. It is common for patients with BN
to have recurrent urinary tract infections. This dysfunction has clinical and
physical relevance in the quality of life of patients affected by it. Based on the
importance of treating bacterial infections that affect patients with BN, it becomes
necessary to search for new therapeutic alternatives, and antimicrobials
originating from plants are presented as a favorable therapeutic practice. The
objective of this research was to perform in vitro and in vivo analyzes of the Ethyl
Acetate fraction from Bixa Orellana leaves (BoEA), and the compound isolated
from the fraction, ellagic acid against microorganisms that cause neurogenic
cystitis in an experimental model of neurogenic bladder in rats, through the
experimental surgical protocol by complete spinal cord transection. The in vitro
results showed that BoEA had a Minimum Inhibitory and Bactericidal
Concentration of 6.25 mg/mL, while ellagic acid, MIC and CBM of 25 mg/mL
against E. coli isolated in the experimental model. In in vivo assays, the BoEA
group (50mg/kg) showed no statistical difference in hematological parameters
when compared to the negative control group. The association group (ellagic acid
with antibiotic) showed greater efficacy among the proposed treatments. As for
urinalysis, the groups treated with ellagic acid and with the association had
substantial improvement in these parameters. In the CFU assay, it can be seen
that all the proposed treatments were able to reduce the number of colonies,
proving the therapeutic efficacy of ellagic acid and its association with antibiotics
for the treatment of E.coli infections. This work can contribute to the process of
searching for therapeutic alternatives with the use of medicinal plants, mainly with
the use of B. orellana and its photochemical compounds for the treatment of
urinary infections resulting from neurogenic bladder.
Instituição: Universidade Federal do Maranhão
Tipo do documento: Dissertação2022-05-06T00:00:00ZCaracterização da coinfecção HIV e hepatite B na população de um hospital de referência em São Luís - MA
https://tedebc.ufma.br/jspui/handle/tede/tede/5112
Título: Caracterização da coinfecção HIV e hepatite B na população de um hospital de referência em São Luís - MA
Autor: SOUZA, Dayse Azevedo Coelho de
Primeiro orientador: AZEVEDO, Conceição de Maria Pedrozo e Silva de
Abstract: The virus that causes hepatitis B (HBV) is a DNA virus belonging to the Hepadnaviridae
family, genus Orthohepadnavirus. It can be transmitted sexually, vertically and
parenterally. Co-infection caused by the human immunodeficiency virus (HIV) and the
hepatitis B virus (HBV) occurs in considerable numbers and is related to the common
transmission route of these viruses. The objective of this work is to characterize co-
infection with the hepatitis B virus among people living with HIV (PLHIV) in a reference
service. It was carried out from January 2022 to July 2023 in a reference hospital in the
state of Maranhão for infectious-parasitic diseases and its population was PLHIV, with a
clinical and serological diagnosis recorded in the medical record, aged 18 years or over,
who were undergoing regular outpatient follow-up at the unit and presented results of
serological markers for Hepatitis B in their medical records. Data were collected from
500 medical records based on the analysis of consultation records, carried out by the
service's multidisciplinary team and compiled into an investigative form. A total of 301
records were included. 263 (87.37%) corresponded to PLHIV and 38 (12.62%) to co-
infected patients (HIV and HBV). Among the co-infected patients, 21(55.26%) were
between 41 and 60 years old, 35(92.11%) were male, 22(57.89%) were mixed race,
17(44.74%) were single, 11 (28.95%) had completed primary education and 38 (100%)
were using antiretroviral therapy with tenofovir. Of the PLHIV, 96 individuals (36.50%)
were vaccinated for hepatitis B. Of these, 37 (38.54%) received the four recommended
doses of the vaccine, 82 (85.42%) had reactive Anti-HBs marker titers and 3(3 .13%) of
these patients presented reactive Anti-HBs due to contact with HBV. In relation to
laboratory tests, it can be seen that in the overall sample the TCD4+ cell count was less
than 350mm3, with 114 (43.35%) in the PLHIV group and 19 (50%) in the group co-
infected with Hepatitis B, while the HIV viral load was above 40 copies/mL, with 211 in
the PLHIV group (80.23%) and 28 in the co-infected group (73.68%). Furthermore, it
was identified that 38 (12.6%) people tested positive for HBsAg, 102 (38.78%) had non-
reactive anti-Hbc, while 143 (54.37%) had reactive results for Anti-Hbc. HBs. As for
HBeAg, 9 (23.68%) of patients co-infected with HIV and HBV had reactive results, while
21 (55.26%) had reactive results for Anti-HBe. Data regarding hepatitis B viral load
indicated that the viral load was less than 2000 IU/ml in 10 (26.32%) of the patients, out
of a total of 17 patients who underwent the test. Investigating the presence of the hepatitis
B virus, by carrying out specific tests, and evaluating the vaccination status for HBV in
PLHIV can play a crucial role in improving the prognosis in this population.
Instituição: Universidade Federal do Maranhão
Tipo do documento: Dissertação2023-11-29T00:00:00Z